Updated on 2024/02/08

写真a

 
MITOH Yoshihiro
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
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Degree

  • Master of Pharmaceutical Science ( Okayama University )

  • Doctor of Philosophy ( Okayama University )

Research Interests

  • Oral Physiology

  • 口腔生理学

Research Areas

  • Life Science / Oral biological science

Education

  • Okayama University   薬学研究科  

    - 1991

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    Country: Japan

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  • Kobe Gakuin University   薬学部  

    - 1988

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    Country: Japan

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Research History

  • - 岡山大学医歯薬学総合研究科 助教

    2004

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  • - Assistant Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2004

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Professional Memberships

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Committee Memberships

  • 日本栄養・食糧学会   会員  

    2019   

  • 日本栄養・食糧学会   会員  

    2019   

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  • International Association for Dental Research   会員  

    2005 - 2006   

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    Committee type:Academic society

    International Association for Dental Research

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  • Society for Neuroscience   会員  

    2000 - 2015   

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    Committee type:Academic society

    Society for Neuroscience

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  • 岡山歯学会   会員  

    1997   

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    Committee type:Academic society

    岡山歯学会

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  • 歯科基礎医学会   会員  

    1994   

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    Committee type:Academic society

    歯科基礎医学会

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  • 日本味と匂学会   評議員  

    1994   

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    Committee type:Academic society

    日本味と匂学会

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  • 日本生理学会   評議員  

    1993   

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    Committee type:Academic society

    日本生理学会

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  • 日本薬学会   会員  

    1988 - 2015   

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    Committee type:Academic society

    日本薬学会

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Papers

  • Distribution of alpha‐synuclein in rat salivary glands

    Tomiko Nishitani, Yoshihiro Mitoh, Takehiro Yajima, Daisuke Tachiya, Tomohiro Hoshika, Tomohiro Fukunaga, Yoshihiro Nishitani, Ryusuke Yoshida, Itaru Mizoguchi, Hiroyuki Ichikawa, Tadasu Sato

    The Anatomical Record   2024.1

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Abstract

    Expression of alpha‐synuclein (Syn), a presynaptic neuronal protein, was immunohistochemically examined in intact rat submandibular, sublingual, and lingual glands. The submandibular gland contained abundant periductal Syn‐immunoreactive (−ir) nerve fibers. Abundant Syn‐ir varicosities were present in acini of the sublingual and serous lingual glands. By confocal laser scanning microscopy, Syn‐ir nerve fibers around smooth muscle actin (SMA)‐ir cells alone were infrequent; however, those around aquaporin‐5 (AQP5)‐ir cells alone and both SMA‐ and AQP5‐ir cells were abundant in the sublingual and serous lingual glands. SMA‐ir cells were occasionally immunoreactive for toll‐like receptor 4, a Syn receptor. Syn‐ir nerve fibers contained tyrosine hydroxylase (TH) in the submandibular gland and choline acetyltransferase (ChAT) in all examined salivary glands. In the superior cervical (SCG), submandibular, and intralingual ganglia, sympathetic and parasympathetic neurons co‐expressed Syn with TH and ChAT, respectively. SCG neurons innervating the submandibular gland contained mostly Syn. In the thoracic spinal cord, 14.7% of ChAT‐ir preganglionic sympathetic neurons co‐expressed Syn. In the superior salivatory nucleus, preganglionic parasympathetic neurons projecting to the lingual nerve co‐expressed Syn and ChAT. The present findings indicate that released Syn acts on myoepithelial cells. Syn in pre‐ and post‐ganglionic neurons may regulate neurotransmitter release and salivary volume and composition.

    DOI: 10.1002/ar.25395

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  • Sugar signals from oral glucose transporters elicit cephalic-phase insulin release in mice Reviewed

    Mitsuhito Takamori, Yoshihiro Mitoh, Kengo Horie, Masahiko Egusa, Takuya Miyawaki, Ryusuke Yoshida

    The Journal of Physiological Sciences   73 ( 1 )   2023.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Cephalic-phase insulin release (CPIR) occurs before blood glucose increases after a meal. Although glucose is the most plausible cue to induce CPIR, peripheral sensory systems involved are not fully elucidated. We therefore examined roles of sweet sensing by a T1R3-dependent taste receptor and sugar sensing by oral glucose transporters in the oropharyngeal region in inducing CPIR. Spontaneous oral ingestion of glucose significantly increased plasma insulin 5 min later in wild-type (C57BL/6) and T1R3-knockout mice, but intragastric infusion did not. Oral treatment of glucose transporter inhibitors phlorizin and phloretin significantly reduced CPIR after spontaneous oral ingestion. In addition, a rapid increase in plasma insulin was significantly smaller in WT mice with spontaneous oral ingestion of nonmetabolizable glucose analog than in WT mice with spontaneous oral ingestion of glucose. Taken together, the T1R3-dependent receptor is not required for CPIR, but oral glucose transporters greatly contribute to induction of CPIR by sugars.

    DOI: 10.1186/s12576-023-00875-3

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    Other Link: https://link.springer.com/article/10.1186/s12576-023-00875-3/fulltext.html

  • Taste Responses and Ingestive Behaviors to Ingredients of Fermented Milk in Mice Reviewed

    Yamase Yuko, Huang Hai, Mitoh Yoshihiro, Egusa Masahiko, Miyawaki Takuya, Yoshida Ryusuke

    Foods   12 ( 6 )   1150   2023.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/foods12061150

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  • 食欲抑制物質の延髄投与による胃の受け入れの能の減弱(Suppression of gastric reservoir function induced by anorexigenic substances in anesthetized rats)

    Kobashi Motoi, Shimatani Yuichi, Fujita Masako, Mitoh Yoshihiro, Yoshida Ryusuke

    The Journal of Physiological Sciences   71 ( Suppl.1 )   156 - 156   2021.8

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    Language:English   Publisher:(一社)日本生理学会  

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  • Orexin A and B in the rat superior salivatory nucleus Reviewed

    Tadasu Sato, Takehiro Yajima, Masako Fujita, Motoi Kobashi, Hiroyuki Ichikawa, Ryusuke Yoshida, Yoshihiro Mitoh

    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL   228   102712 - 102712   2020.11

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.autneu.2020.102712

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  • The Effects of Mutual Interaction of Orexin-A and Glucagon-Like Peptide-1 on Reflex Swallowing Induced by SLN Afferents in Rats Reviewed

    Motoi Kobashi, Yuichi Shimatani, Masako Fujita, Yoshihiro Mitoh, Ryusuke Yoshida, Ryuji Matsuo

    International Journal of Molecular Sciences   21 ( 12 )   4422 - 4422   2020.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    (1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague–Dawley rats under urethane–chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested.

    DOI: 10.3390/ijms21124422

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  • Effects of bitter receptor antagonists on behavioral lick responses of mice Reviewed

    Michimasa Masamoto, Yoshihiro Mitoh, Motoi Kobashi, Noriatsu Shigemura, Ryusuke Yoshida

    Neuroscience Letters   730   135041 - 135041   2020.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.neulet.2020.135041

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  • 麻酔ラットの反射嚥下に対するオレキシン-Aとグルカゴン様ペプチド-1の相互作用(Mutual interaction of orexin-A and glucagon-like peptide-1 on reflex swallowing in anesthetized rats)

    Kobashi Motoi, Shimatani Yuichi, Fujita Masako, Mitoh Yoshihiro, Matsuo Ryuji

    The Journal of Physiological Sciences   69 ( Suppl.1 )   S116 - S116   2019.6

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    Language:English   Publisher:(一社)日本生理学会  

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  • 麻酔下ラットではglucagon-like peptide-1がorexin-Aによる嚥下反射抑制作用を減弱する(Glucagon-like peptide-1 diminishes the suppressive effect of orexin-A on the reflex swallowing in anesthetized rats)

    Kobashi Motoi, Shimatani Yuichi, Fujita Masako, Mitoh Yoshihiro, Matuo Ryuji

    The Journal of Physiological Sciences   68 ( Suppl.1 )   S121 - S121   2018.3

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    Language:English   Publisher:(一社)日本生理学会  

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  • Effects of cevimeline on excitability of parasympathetic preganglionic neurons in the superior salivatory nucleus of rats Reviewed

    Yoshihiro Mitoh, Hirotaka Ueda, Hiroyuki Ichikawa, Masako Fujita, Motoi Kobashi, Ryuji Matsuo

    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL   206   1 - 7   2017.9

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.autneu.2017.05.010

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  • Central glucagon like peptide-1 inhibits reflex swallowing elicited by the superior laryngeal nerve via caudal brainstem in the rat Reviewed

    Motoi Kobashi, Satoshi Mizutani, Masako Fujita, Yoshihiro Mitoh, Yuichi Shimatani, Ryuji Matsuo

    BRAIN RESEARCH   1671   26 - 32   2017.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    The effects of glucagon like peptide-1 (GLP-1) on reflex swallowing were examined using anaesthetized rats. GLP-1 was injected into the dorsal vagal complex (DVC) using glass micropipettes. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated in the mylohyoide muscle through bipolar electrodes. Microinjection of GLP-1 into the medial DVC (M-DVC) increased the frequency of swallowing during the electrical stimulation of the SLN and extended the latency of the first swallowing. Microinjection of GLP-1 into the lateral DVC (L-DVC) did not change the frequency of swallowing or the latency of the first swallowing. Neither the injection of vehicle into the M-DVC nor L-DVC affected swallowing frequency. Pre-injection of exendin (5-39), a GLP-1 receptor antagonist, attenuated the degree of suppression of swallowing frequency induced by the administration of GLP-1 in addition to shortening the latency of the first swallowing. To identify the effective site of GLP-1, lesion experiments were performed. Electrical lesion of the commissural part of the NTS (cNTS) and the vacuum removal of the area postrema (AP) did not affect the inhibition of reflex swallowing induced by the injection of GLP-1 into the M-DVC. Electrical lesion of the medial nucleus of the NTS (mNTS) and its vicinity abolished the inhibitory effects of swallowing induced by the injection of GLP-1. These results suggest that GLP-1 inhibits reflex swallowing via the mNTS in the dorsal medulla. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2017.07.004

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  • オレキシンAはGLP-1による嚥下減弱作用を抑制する(Orexin-A diminishes the suppressive effect of GLP-1 on the reflex swallowing)

    Kobashi Motoi, Shimatani Yuichi, Fujita Masako, Mitoh Yoshihiro, Matsuo Ryuji

    The Journal of Physiological Sciences   67 ( Suppl.1 )   S106 - S106   2017.3

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  • Aflatoxins in Rice Artificially Contaminated with Aflatoxin-producing Aspergillus flavus under Natural Storage in Japan Reviewed

    Satoshi Sugihara, Hiroyuki Doi, Masahiko Kato, Yoshihiro Mitoh, Toshihide Tsuda, Satoru Ikeda

    ACTA MEDICA OKAYAMA   70 ( 3 )   167 - 173   2016.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OKAYAMA UNIV MED SCHOOL  

    Aflatoxin (AFT) contamination is frequent in foods grown in tropical regions, including rice. Although AFTs are generally not found in temperate-region foods, global warming has affected typical temperate-region climates, potentially permitting the contamination of foods with AFT-producing Aspergillus flavus (A. flavus). Here we investigated the AFT production in rice during storage under natural climate conditions in Japan. We examined AFTs in brown rice and rough rice artificially contaminated with A. flavus for 1 year in Japan, and we subjected AFTs in white rice to the same treatment in airtight containers and examined the samples in warm and cold seasons, simulating the storage of white rice in general households. In the brown rice, AFTs increased after 2 months (March) and peaked after 9 months (October). The AFT contamination in the rough rice was minimal. After the polishing and cooking of the brown rice, AFTs were undetectable. In the white rice stored in airtight containers, AFTs increased after 1 month (August) and peaked after 2 months (September). Minimal AFTs were detected in the cold season. Thus, AFT contamination in rice may occur in temperate regions following A. flavus contamination. The storage of rice as rough rice could provide be useful for avoiding AFT contamination.

    DOI: 10.18926/AMO/54415

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  • Identification of the effective site of GLP-1 to suppress reflex swallowing Reviewed

    Satoshi Mizutani, Motoi Kobashi, Yuichi Shimatani, Masako Fujita, Yoshihiro Mitoh, Masatoshi Mizutani, Ryuji Matsuo

    CHEMICAL SENSES   40 ( 8 )   589 - 589   2015.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:OXFORD UNIV PRESS  

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  • Orexin-A inhibits the action of GLP-1 on the reflex swallowing Reviewed

    Kobayashi Motoi, Mizutani Satoshi, Fujita Masako, Mitoh Yoshihiro, Shimatani Yuichi, Matsuo Ryuji

    The Japanese journal of taste and smell research   22 ( 3 )   371 - 374   2015

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Association for the Study of Taste and Smell  

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    Other Link: http://search.jamas.or.jp/link/ui/2016233777

  • Central orexin inhibits reflex swallowing elicited by the superior laryngeal nerve via caudal brainstem in the rat Reviewed

    Motoi Kobashi, Satoshi Mizutani, Masako Fujita, Yoshihiro Mitoh, Yuichi Shimatani, Ryuji Matsuo

    PHYSIOLOGY & BEHAVIOR   130   6 - 12   2014.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    We examined the effects of orexins on the reflex swallowing using anesthetized rats. Orexins were administered into the fourth ventricle. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated the mylohyoid muscle through bipolar electrodes. The frequency of swallowing during the electrical stimulation of the SLN decreased after the administration of orexin-A in a dose-dependent manner. The latency of the first swallowing tended to be extended after the administration of orexin-A. The administration of orexin-B did not affect swallowing frequency. Pre-administration of SB334867, an orexin-1 receptor antagonist, attenuated the degree of inhibition of swallowing frequency induced by the administration of orexin-A. To identify the effective site of orexin-A, the effect of a microinjection of orexin-A into the dorsal vagal complex (DVC) was evaluated. Orexin-A was injected into one of the lateral DVC, the intermediate DVC, or the medial DVC. Microinjection of orexin-A into the medial DVC but not the other two sites decreased swallowing frequency. Pre-injection of SB334867 into the medial DVC disrupted the inhibitory response induced by fourth ventricular administration of orexin-A. The electrical lesion of the commissural part of the NTS, but not ablation of the AP, abolished the inhibition of reflex swallowing induced by fourth ventricular administration of orexin-A. These results suggest that orexin-A inhibits reflex swallowing via orexin-1 receptors situated in the commissural part of the NTS and/or its vicinity. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.physbeh.2014.03.009

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  • Differential involvement of two cortical masticatory areas in submandibular salivary secretion in rats Reviewed

    Naoto Maeda, Motoi Kobashi, Yoshihiro Mitoh, Masako Fujita, Shogo Minagi, Ryuji Matsuo

    BRAIN RESEARCH   1543   200 - 208   2014.1

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    To evaluate the role of the masticatory area in the cerebral cortex in the masticatory-salivary reflex, we investigated submandibular salivary secretion, jaw-movement trajectory and electromyographic activity of the jaw-opener (digastric) and jaw-closer (masseter) muscles evoked by repetitive electrical stimulation of the cortical masticatory area in anesthetized rats. Rats have two cortical masticatory areas: the anterior area (A-area) in the orofacial motor cortex, and the posterior area (P-area) in the insular cortex. Our defined P-area extended more caudally than the previous reported one. P-area stimulation induced vigorous salivary secretion (about 20 mu l/min) and rhythmical jaw movements (3-4 Hz) resembling masticatory movements. Salivary flow persisted even after minimizing jaw movements by curarization. A-area stimulation induced small and fast rhythmical jaw movements (6-8 Hz) resembling licking of solutions, but not salivary secretion. These findings suggest that P-area controls salivary secretion as well as mastication, and may be involved in the masticatory-salivary reflex. (C) 2013 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2013.11.024

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  • Role of the lateral hypothalamus in submandibular salivary secretion during feeding in rats.(共著) Reviewed

    Matsuo R, Kobashi M, Mitoh Y, Fujita M

    Brain Research   1596   99 - 107   2014

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    DOI: 10.1016/j.brainres.2014.11.026.

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  • GLP-1中枢投与による反射性嚥下抑制を惹起する部位の同定(共著) Reviewed

    水谷諭史, 小橋基, 島谷祐一, 藤田雅子, 美藤純弘, 水谷雅年, 松尾龍二

    日本味と匂学会誌   21 ( 3 )   245 - 248   2014

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    著者らは前回、GLP-1(Glucagon-like peptide-1)が背側迷走神経複合核群正中部(M-DVC)を介して反射性嚥下を抑制することを報告した。今回、GLP-1がM-DVC領域のどの部位に作用して反射性嚥下を抑制するのかを明らかにするため、ラットを用いて、M-DVC中の異なる3部位を破壊し、GLP-1微量注入に対する反応を調べた。その結果、GLP-1はM-DVCのうち孤束核内側部のGLP-1受容体を介して反射性嚥下を抑制することが示唆された。

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J04102&link_issn=&doc_id=20150212090007&doc_link_id=%2Fcw7jasts%2F2014%2F002103%2F010%2F0245-0248%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2014%2F002103%2F010%2F0245-0248%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • GLP-1 modulates reflex swallowing of the rat Reviewed

    Mizutani Satoshi, Kobashi Motoi, Fujita Masako, Mitoh Yoshihiro, Shimatani Yuichi, Matsuo Ryuji

    The Japanese journal of taste and smell research   20 ( 3 )   237 - 240   2013

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Association for the Study of Taste and Smell  

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    Other Link: http://search.jamas.or.jp/link/ui/2014158479

  • オレキシン-Aによる反射性嚥下抑制を惹起する中枢作用部位の検討.(共著) Reviewed

    水谷諭史, 小橋基, 藤田雅子, 美藤純弘, 島谷祐一, 松尾龍二

    日本味と匂学会誌   19 ( 3 )   365 - 368   2012

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    オレキシン-Aによる反射性嚥下抑制を惹起する中枢作用部位について検討するため、ラットを用いて背側迷走神経核群のうち嚥下起動神経群の存在する孤束周辺の孤束核とその周囲部(外側部)、孤束核中央部とその周辺部(中間部)、最後野とその下部の孤束核交連部(正中部)の3部位にオレキシン-Aを微量注入し、嚥下回数を比較した。その結果、正中部でのみ嚥下回数の有意な減少が観察され、中間部および外側部では有意差がなかった。正中部にオレキシン1受容体アンタゴニストSB334867を前注入することで、オレキシン-Aの第四脳室内滴下投与による嚥下頻度の変化は認めなかった。また反射性嚥下抑制に関与している部分を明らかにするため、延髄背側迷走神経核正中部の最後野吸引除去後または孤束核交連部電気焼灼後にオレキシン-Aを投与したところ、無破壊群と最後野吸引除去群との間に有意差はなかったが、孤束核交連部電気焼灼群との間には有意差が認められた。

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  • Muscarinic receptor immunoreactivity in the superior salivatory nucleus neurons innervating the salivary glands of the rat Reviewed

    Hirotaka Ueda, Yoshihiro Mitoh, Masako Fujita, Motoi Kobashi, Takashi Yamashiro, Tomosada Sugimoto, Hiroyuki Ichikawa, Ryuji Matsuo

    NEUROSCIENCE LETTERS   499 ( 1 )   42 - 46   2011.7

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    The superior salivatory nucleus (SSN) contains preganglionic parasympathetic neurons to the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor agonist, stimulates the salivary glands and is presently used as sialogogue in the treatment of dry mouth. Since cevimeline passes through the blood-brain barrier, it is also able to act on muscarinic acetylcholine receptors in the central nervous system. Our preliminary experiment using the whole-cell patch-clamp technique has shown that cevimeline excites SSN neurons in rat brain slices, suggesting that SSN neurons have muscarinic acetylcholine receptors; however, it is unclear which subtypes of muscarinic acetylcholine receptors exist in SSN neurons. In the present study, we investigated immunohistochemically muscarinic acetylcholine receptor subtypes, M1 receptor (M1R), M2R, M3R, M4R, and M5R in SSN neurons. SSN neurons innervating the salivary glands, retrogradely labeled with a fluorescent tracer from the chorda-lingual nerve, mostly expressed M3R immunoreactivity (-ir) (92.3%) but not M1R-ir. About half of such SSN neurons also showed M2R- (40.1%), M4R- (54.0%) and M5R-ir (46.0%); therefore, it is probable that SSN neurons co-express M3R-ir with at least two of the other muscarinic receptor subtypes. This is the first report to show that SSN neurons contain muscarinic acetylcholine receptors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2011.05.029

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  • オレキシン中枢投与による嚥下反射の抑制.(共著) Reviewed

    水谷諭史, 小橋基, 藤田雅子, 美藤純弘, 島谷祐一, 松尾龍二

    日本味と匂学会誌   18 ( 3 )   327 - 330   2011

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    上喉頭神経由来の反射性嚥下に及ぼすオレキシン中枢投与の効果を、ウレタン・クロラロース麻酔下のラットを用いて検討した。オレキシンAの第四脳室内滴下投与により、上喉頭神経由来の反射性嚥下が抑制されることが明らかになった。オレキシン1受容体への親和性がオレキシンAよりも低いオレキシンBの第四脳室内滴下投与では、反射性嚥下の抑制は認められなかった。また、オレキシン1受容体アンタゴニストであるSB334867の第四脳室内前投与により、反射性嚥下の抑制が消失した。以上より、オレキシンA投与による反射性嚥下の抑制は、延髄背側部のオレキシン1受容体を介して発現することが示唆された。

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  • Central ghrelin inhibits reflex swallowing elicited by activation of the superior laryngeal nerve in the rat Reviewed

    Motoi Kobashi, Song-Yu Xuan, Masako Fujita, Yoshihiro Mitoh, Ryuji Matsuo

    REGULATORY PEPTIDES   160 ( 1-3 )   19 - 25   2010.2

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    The effect of ghrelin on rhythmic reflex swallowing was examined in urethane-chloralose anesthetized rats. Swallowing was monitored by recording electromyographic activities of the suprahyoid muscle. Fourth ventricular administration of ghrelin decreased swallowing frequency during electrical stimulation of the central cut end of the superior laryngeal nerve (SLN stimulation). A significant decrease in swallowing frequency was observed after ghrelin administration at doses of 3, 10, 30 and 100 pmol. The administration of ghrelin with growth hormone secretagogue receptor antagonist ([D-Lys(3)] GHRP-6) did not change swallowing frequency during SLN stimulation. Neither mean blood pressure nor heart rate changed after the administration of 10 pmol ghrelin. Bilateral vagotomy did not disrupt the ghrelin response. These observations indicate that the ghrelin response does not depend on either cardiovascular OF abdominal responses. Microinjection of ghrelin (0.3 pmol) into the vicinity of the solitary tract inhibited swallowing induced by SLN stimulation. Fourth ventricular administration of orexin-A (3 nmol) also inhibited reflex swallowing elicited by SLN stimulation. These results suggest that ghrelin and other orexigenic peptides inhibit reflex swallowing by modifying neural activities of the dorsal medulla where the swallowing center is housed. (C) 2009 Elsevier B.V. All rights reserved.

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  • Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat Reviewed

    Motoi Kobashi, Mamoru Yanagihara, Masako Fujita, Yoshihiro Mitoh, Ryuji Matsuo

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   296 ( 2 )   R217 - R223   2009.2

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    Kobashi M, Yanagihara M, Fujita M, Mitoh Y, Matsuo R. Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat. Am J Physiol Regul Integr Comp Physiol 296: R217-R223, 2009. First published November 26, 2008; doi: 10.1152/ajpregu.00878.2007.-The effects of fourth ventricular administration of ghrelin on motility of the proximal stomach were examined in anesthetized rats. Intragastric pressure (IGP) was measured using a balloon situated in the proximal part of the stomach. Administration of ghrelin into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Significant reduction of IGP was observed at doses of 3, 10, or 30 pmol. The administration of ghrelin (10 or 30 pmol) with growth hormone secretagogue receptor (GHS-R) antagonist ([D-Lys(3)] GHRP-6; 1 nmol) into the fourth ventricle did not induce a significant change in IGP. The sole administration of [D-Lys(3)] GHRP-6 also did not induce a significant change in IGP. Bilateral sectioning of the vagi at the cervical level abolished the relaxation induced by the administration of ghrelin (10 or 30 pmol) into the fourth ventricle, suggesting that relaxation induced by ghrelin is mediated by vagal preganglionic neurons. Microinjections of ghrelin (200 fmol) into the caudal part of the dorsal vagal complex (DVC) induced obvious relaxation of the proximal stomach. Similar injections into the intermediate part of the DVC did not induce significant change. Dose-response analyses revealed that the microinjection of 2 fmol of ghrelin into the caudal DVC significantly reduced IGP. These results revealed that ghrelin induced relaxation in the proximal stomach via GHS-R situated in the caudal DVC.

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  • Postnatal development of inhibitory synaptic transmission to superior salivatory neurons in rats

    Yoshihiro Mitoh, Makoto Funahashi, Masako Fujita, Motoi Kobashi, Ryuji Matsuo

    Journal of Medical Investigation   56 ( 1 )   270 - 272   2009

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    The primary parasympathetic center of the submandibular and sublingual salivary glands is the superior salivatory (SS) nucleus, and its neurons receive excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) synaptic transmissions in rats. In the present study, we focused on the postnatal development of inhibitory transmission to SS neurons. Gramicidin-perforated whole-cell patch-clamp recordings were performed in rat brainstem slices on postnatal day 2 (P2)-P14. Developmental changes in the intracellular Cl - concentration ([Cl-]in) were examined based on the reversal potentials of total inhibitory postsynaptic currents (GABAergic plus glycinergic), which were evoked by electrical stimulation near the recording neuron. The [Cl-]in in the P8-P14 groupwas significantly lower than in the P2-P7 group. The effect of GABA application at the resting potentials changed from depolarization to hyperpolarization around P8, suggesting that SS neurons acquired mature inhibitory systems around P8. The period at which GABA responses change from excitatory to inhibitory in SS neurons was discussed compared with those of the forebrain, brainstem, and spinal neurons.

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  • Cevimeline enhances the excitability of rat superior salivatory neurons

    Hirotaka Ueda, Yoshihiro Mitoh, Hiroyuki Ichikawa, Motoi Kobashi, Takashi Yamashiro, Ryuji Matsuo

    Journal of Medical Investigation   56 ( 1 )   267 - 269   2009

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    Cevimeline, a therapeutic drug for xerostomia, is an agonist of muscarinic acetylcholine receptors (mAChRs), and directly stimulates the peripheral mAChRs of the salivary glands. Since cevimeline is distributed in the brain after its oral administration, it is possible that it affects the central nervous system. However, it is unknown how cevimeline affects the superior salivatory (SS) neurons, which control submandibular salivation. In the present study, we examined the effects of cevimeline on the SS neurons using the whole-cell patch-clamp technique in brain slices. In Wistar rats (6-10 days), the SS neurons were retrogradely labeled by Texas Red applied to the chorda-lingual nerve. Two days after injection, whole-cell recordings were obtained from the labeled cells, and miniature excitatory postsynaptic currents (mEPSCs) were examined. Cevimeline induced the inward currents dose-dependently and increased the frequency of mEPSCs. Therefore, it is suggested that cevimeline enhances the excitability via post- and presynaptic muscarinic receptors in the rat SS neurons. In conclusion, cevimeline may enhance the excitability of the SS neurons.

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  • Immunohistochemical study on the distribution and origin of GABAergic nerve terminals in the superior salivatory nucleus

    Ayumi Matsushima, Hiroyuki Ichikawa, Masako Fujita, Yoshihiro Mitoh, Motoi Kobashi, Takashi Yamashiro, Ryuji Matsuo

    Journal of Medical Investigation   56 ( 1 )   264 - 266   2009

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    The superior salivatory nucleus (SSN) is the primary parasympathetic center controlling submandibular salivatory secretion. Our previous electrophysiological study revealed that many SSN neurons receive GABAergic and glycinergic synaptic inputs. In the present study, we examined the distribution of GABAergic and glycinergic nerve terminals, GABAA receptors in the SSN, and the origin of GABAergic nerve terminals innervating the SSN. Glutamic acid decarboxylase (GAD) and glycine transporter 2 (GLYT2) were used as markers of GABAergic and glycinergic nerve terminals, respectively. GAD-and GLYT2-positive nerve terminals and GABAA receptors were examined immunohistochemically in SSN neurons labeled by the retrograde axonal transport of FastBlue (FB) injected into the chorda-lingual nerve. The SSN neurons abundantly contained GAD-positive nerve terminals and GABAA receptors, suggesting that SSN neurons undergo strong GABAergic inhibition. The origin of GABAergic terminals was examined in neurons labeled by the retrograde transport of FluoroGold (FG) injected into the SSN. GAD was used as a marker of GABAergic neurons. Numerous FG-labeled neurons were found in the forebrain and brainstem. However, in FG-labeled neurons, GAD-positive neurons were occasionally observed in the reticular formation of the brainstem. These findings suggest that SSN neurons mainly receive GABAergic projections from the reticular formation.

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  • Development of inhibitory synaptic transmission to the superior salivatory nucleus in rats Reviewed

    Yoshihiro Mitoh, Makoto Funahashi, Akihito Fujii, Masako Fujita, Motoi Kobashi, Ryuji Matsuo

    BRAIN RESEARCH   1191   47 - 54   2008.1

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    The primary parasympathetic center of the submandibular and sublingual salivary glands is the superior salivatory (SS) nucleus, neurons of which receive excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) synaptic transmissions in rats. In the present study, to examine postnatal neural development, we focused on inhibitory transmission to the SS neurons in neonatal rats from postnatal day 2 (P2) to P14. Conventional and gramicidin-perforated whole-cell patch-clamp techniques were applied to the neurons in brainstem slices. The decay time constants of GABAergic and glycinergic postsynaptic currents (PSCs) consisted of fast (tau(fast)) and slow (tau(slow)) components. Both tau(fast) and tau(slow) of PSC Components tended to become faster with development. The equilibrium potential of Cl- (Ecl-) was estimated from the reversal potentials of total PSCs (GABAergic plus glycinergic). The Ecl- in the P8-P14 group was significantly more negative than Ecl- in the P2-P7 group. Exogenous GABA application at the resting potentials produced depolarization in 83% of SS neurons at P2-P7 and accompanied the action potential in some neurons. In contrast, at P8-P14, GABA evoked hyperpolarization in 78% of SS neurons; therefore, SS neurons did not acquire mature inhibitory systems until P14. The development of SS neurons is discussed as compared with the development of peripheral salivary gland tissue and brainstem neurons that participate in oral motor and sensory functions. (c) 2007 Elsevier B.V. All rights reserved.

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  • Purinergic modulation of area postrema neuronal excitability in rat brain slices Reviewed

    Naoki Kodama, Makoto Funahashi, Yoshihiro Mitoh, Shogo Minagi, Ryuji Matsuo

    Brain Research   1165 ( 1 )   50 - 59   2007.8

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    ATP has been shown to excite neurons in various regions of the central nervous system. Whereas immunohistochemical studies show P2X receptors in the area postrema, the responsiveness of area postrema neurons to extracellular ATP has not been studied. To investigate the effects of purinoceptor activation on area postrema neuronal excitability, we performed whole-cell recordings from area postrema neurons in rat brain slices. Most area postrema neurons responded to ATP application, and most responses were excitatory. Voltage-clamp recordings showed three different types of response: (1) a postsynaptic or extrasynaptic excitatory response (inward currents
    n = 26/51 cells), (2) a presynaptic excitatory response (increased frequency of miniature excitatory postsynaptic currents with only a small direct postsynaptic current
    n = 24/51 cells, or (3) a postsynaptic inhibitory response (outward current
    n = 1/51). The excitatory responses were found in both of the two major electrophysiological cell classes, i.e. cells displaying Ih and cells not displaying Ih, while the inhibitory responses were found in only cells not displaying Ih. Current-clamp recordings showed ATP-induced depolarization (n = 13/15) or hyperpolarization (n = 2/15) of membrane potential that modulated the frequency of action potentials. In the presence of CNQX, mEPSCs were abolished and bath-applied ATP did not generate mEPSCs, indicating that glutamate release was facilitated by the activation of presynaptically located ATP receptors. Our pharmacological results from studies with ATP, αβme-ATP, βme-ATP and PPADS indicate that the post- and/or extrasynaptic responses are most likely mediated by P2X7 receptors and/or receptors composed of P2X2 and P2X5 subunits. We conclude that half of the presynaptic responses are most likely mediated by P2X7 receptors and/or receptors composed of P2X2 and P2X5 subunits while the others also contain P2X1 subunits. It is well known that P2X7 subunit forms only homomultimeric P2X receptors. Finally, the present study suggests that purinoceptor activation may contribute to the control of several autonomic functions by area postrema neurons. © 2007 Elsevier B.V. All rights reserved.

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  • ラット脳スライス標本における延髄最後野ニューロンのセビメリンによる興奮性応答

    兒玉 直紀, 舩橋 誠, 美藤 純弘, 松尾 龍二

    Journal of Oral Biosciences   49 ( Suppl. )   119 - 119   2007.8

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  • ラット孤束膠様核ニューロンのニコチン感受性

    舩橋 誠, 兒玉 直紀, 美藤 純弘, 松尾 龍二, 赤池 忠

    日本生理学雑誌   69 ( 6 )   241 - 241   2007.6

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  • 上喉頭神経由来の反射性嚥下におよぼす中枢グレリンの調節作用.(共著) Reviewed

    小橋基, 玄松玉, 美藤純弘, 藤田雅子, 松尾龍二

    日本味と匂学会誌   14 ( 3 )   365 - 368   2007

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    上喉頭神経惹起性嚥下におよぼすグレリン中枢投与の効果を、ウレタン・クロラロース麻酔下のラットを用いて検討した。ウレタン・クロラロース麻酔下のSD系雄性ラットを用いた。上喉頭神経中枢端を電気刺激することにより嚥下反射を惹起し、顎舌骨筋に刺入した双極形釣針電極により筋電図を導出し嚥下をモニターした。グレリンの第四脳室内滴下投与後には、上喉頭神経刺激により惹起された嚥下の回数の減少を観察した。第四脳室内へのグレリン受容体アンタゴニスト単独投与により嚥下の回数に有意な変化は認めなかった。孤束周辺の延髄背側部にグレリンを微量注入し、嚥下回数は有意に減少した。初回嚥下の潜時もグレリン微量注入10分後に有意な延長を認めた。オレキシンAの投与により嚥下回数の有意な減少を観察した。

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  • プリン作動性受容体を介するラット最後野ニューロン活動の修飾

    兒玉 直紀, 舩橋 誠, 美藤 純弘, 松尾 龍二

    Journal of Oral Biosciences   48 ( Suppl. )   132 - 132   2006.9

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  • 最後野内ニコチン局所投与により誘発される孤束膠様核ニューロンの興奮性応答

    舩橋 誠, 兒玉 直紀, 美藤 純弘, 松尾 龍二, 赤池 忠

    Journal of Oral Biosciences   48 ( Suppl. )   188 - 188   2006.9

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  • Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat Reviewed

    M Kobashi, Y Shimatani, K Shirota, SY Xuan, Y Mitoh, R Matsuo

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   290 ( 2 )   R290 - R297   2006.2

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    Effects of neuropeptide Y (NPY) on motility of the proximal stomach was examined in anesthetized rats. Intragastric pressure was measured using a balloon situated in the proximal part of the stomach. Administration of NPY into the fourth ventricle induced relaxation of the proximal stomach in a dosedependent manner. Administration of an Y1 receptor (Y1R) agonist [Leu(31), Pro(34)] NPY induced a larger relaxation than NPY. The administration of an Y2 receptor agonist (NPY 13-36) did not induce significant changes in motility. Microinjections of [Leu(31), Pro(34)] NPY into the caudal part of the dorsal vagal complex (DVC) induced relaxation of the proximal stomach. In contrast, similar injections into the intermediate part of the DVC increased IGP of the proximal stomach. Administration of NPY into the fourth ventricle did not induce relaxation after bilateral injections of the Y1R antagonist (1229U91) into the caudal DVC. These results indicate that NPY induces relaxation in the proximal stomach via Y1Rs situated in the DVC. Because bilateral vagotomy below the diaphragm abolished the relaxation induced by the administration of NPY into the fourth ventricle, relaxation induced by NPY is probably mediated by vagal preganglionic neurons. Intravenous injection of atropine methyl nitrate reduced relaxation induced by administration of NPY. Therefore, relaxation induced by NPY is likely mediated by peripheral cholinergic neurons.

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  • Variety of morphological and electrophysiological properties of area postrema neurons in adult rat brain slices Reviewed

    M Funahashi, Y Mitoh, T Akaike, R Matsuo

    NEUROSCIENCE RESEARCH   54 ( 1 )   43 - 48   2006.1

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    Whole-cell recordings were performed to examine the morphological properties of electrophysiologically classified area postrema (AP) neurons in rat brain slices. Using electrophysiological criteria, AP neurons were subdivided into three groups: (1) cells displaying both the hyperpolarization-activated cation current (I-h) and the fast transient outward current (fast It,); (2) cells displaying only the (fast I-to) (3) cells displaying only the slow I-to. All AP neurons had a single axon that was distinctly thinner than the cells' dendrites. No systematic differences, across groups, in the orientation of dendrites, or axons were identified. Mean values of cell size and capacitance of neurons from group 3 were significantly larger than those of the other groups. Interestingly, a number of cells from groups 1 and 3 but not group 2 were found to extend their dendrites into the nucleus tractus solitarius (NTS), suggesting that AP neurons could receive vagal afferent inputs at their dendritic termini within the NTS. Although the AP has been implicated to contain uniformly shaped neurons, this study indicates the presence of significantly different subpopulations of AP neurons, which were characterized not only electrophysiologically but also morphologically. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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  • Central neuropeptide Y induces gastric relaxation via Y1 receptors in the dorsal vagal complex of the rats Reviewed

    M Kobashi, K Shirota, SY Xuan, Y Shimatani, Y Mitoh, R Matsuo

    CHEMICAL SENSES   31 ( 1 )   J4 - J4   2006.1

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  • グレリン中枢投与による胃近位部食物受け入れ機能の促進作用.(共著) Reviewed

    小橋基, 柳原衞, 玄松玉, 美藤純弘, 松尾龍二

    日本味と匂学会誌   13 ( 3 )   509 - 512   2006

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    グレリンはグレリン受容体(GHS-R)の内因性リガンドとして胃組織から見いだされ、強い摂食亢進作用を持つことが明らかとなっている。グレリンを迷走神経背側複合核群に作用させるために第四脳室内に滴下投与し、胃近位部の収縮性について検討した。グレリンの第四脳室内投与により胃近位部が弛緩し、延髄のGHS-Rを介した応答であると考えられた。グレリンは、側脳室のみならず第四脳室内投与でも摂食の亢進を惹起した。胃遠位部律動収縮亢進よりも、近位部弛緩の方がより低用量のグレリン投与で惹起された。12時間の明暗周期で飼育されたラットでは、血中グレリン濃度は摂食を行わない明期の間にピークを持った。

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  • ラット最後野ニューロンの機能と形態

    舩橋 誠, 美藤 純弘, 兒玉 直紀, 松尾 龍二, 赤池 忠

    日本生理学雑誌   67 ( 12 )   400 - 400   2005.12

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  • The origin of sensory nerve fibers that innervate the submandibular salivary gland in the rat Reviewed

    M Kobashi, H Ichikawa, M Kobashi, M Funahashi, Y Mitoh, R Matsuo

    BRAIN RESEARCH   1060 ( 1-2 )   184 - 187   2005.10

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    The origin of sensory nerves that innervate the submandibular salivary gland was investigated in the rat. After application of wheat germ agglutinin-horseradish peroxidase to the cut endings of the sympathetic and parasympathetic nerve branches at the hilus of the gland, labeled cells were mainly found in the dorsal root ganglia and the trigeminal ganglion, respectively. The labeled neurons in these ganglia were of various sizes compared to unlabeled neurons, suggesting that the sensory nerves of the gland conduct various modalities of sensory information. (c) 2005 Elsevier B.V. All rights reserved.

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  • 最後野におけるプリン受容体(P2X)による神経活動の修飾

    兒玉 直紀, 舩橋 誠, 美藤 純弘, 松尾 龍二

    Journal of Oral Biosciences   47 ( Suppl. )   113 - 113   2005.9

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  • 孤束膠様核単一ニューロンの形態的特徴,膜特性および化学感受性

    舩橋 誠, 美藤 純弘, 兒玉 直紀, 松尾 龍二, 赤池 忠

    Journal of Oral Biosciences   47 ( Suppl. )   175 - 175   2005.9

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  • ニューロペプチドY-Y1受容体を介した胃近位部の食物受け入れ応答.(共著) Reviewed

    小橋 基, 城田惠祐, 玄 松玉, 島谷祐一, 美藤純弘, 松尾龍二

    日本味と匂学会誌   12 ( 3 )   239 - 242   2005

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    ニューロペプチドY(NPY)が胃遠位部の律動収縮を調節することは明らかとなっているが,胃弛緩に関与するかどうかは明らかとなっていない.そこで,食物貯留部位である胃の近位部の弛緩に中枢のNPYが関与するか,またその作用機序を検討した.胃近位部でNPY由来の弛緩が出現するのを確認したラットに,腹部迷走神経両側切断を施した.切断後,再びNPYを第4脳室に投与しその応答を検討した.切断前に見られた胃内圧の有意な減少は切断後には観察しなかった.硝酸メチルアトロピンの静脈内投与がNPY由来の胃近位部弛緩に及ぼす効果を調べた.アトロピン静注前に見られたNPY由来の有意な胃内圧減少はアトロピン静注後には観察しなかった

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  • Activation of presynaptic 5-HT3 receptors facilities glutamatergic synaptic inputs to area postrema neurons in rat brain slices Reviewed

    M Funahashi, Y Mitoh, R Matsuo

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   26 ( 8 )   615 - 622   2004.10

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    Whole-cell voltage-clamp recordings were performed to investigate the serotonergic modulation of neurotransmitter release onto rat area postrenia neurons in vitro. The bath application of serotonin (5-HT- 50 muM) or phenylbiguanide (PBA; 50 mum), a potent 5-HT, receptor agonist, increased the frequency of spontaneous excitatory, postsynaptic currents (sEPSCs) or miniature EPSCs (inEPSCs) in 35 of 83 neurons (42%). These increases occurred in all electrophysiological cell classes. No cells exhibited a decrease in EPSC frequency The majority of responding cells showed no inward currents during the application of serotonergic agonists (n = 34135). However, the amplitude of mEPSCs was increased in 11/11 cells with 5-HT or 3111 cells with PBA. ICS-205,930, a potent 5-HT3 receptor antagonist, markedly, suppressed the 5-HT-inducedjacilitation of sEPSCs (n = 5) or mEPSCs (it = 5). An increase in the frequency of mEPSCs after PBA exposure was found, even with media containing Cd2+ (50 muM) or zero Ca2+. mEPSCs and evoked EPSCs were completely, blocked in media containing the non-NMDA ionotropic receptor antagonist, CNQX (10 muM), indicating that EPSCs were glutamate events. These results suggest that glutamate release is increased in the area postrenia by presynaptic 5-HT, receptor activation. Furthermore, we present evidence that 5-HT, receptor activation may be able to directly release glutamate from terminals, bypassing a requirement for voltage-dependent calcium entry into terminals. Such a mechanism may contribute to the chemosensitive function of area postrema neurons. (C) 2004 Prous Science. All rights reserved.

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  • Nicotinic modulation of area postrema neuronal excitability in rat brain slices Reviewed

    M Funahashi, Y Mitoh, R Matsuo

    BRAIN RESEARCH   1017 ( 1-2 )   227 - 233   2004.8

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    We investigated the functions of nicotinic receptor activation on area postrema neurons by making whole-cell recordings in rat brainstem slices. Excitatory responses to nicotine application were found in approximately 78% (35/45) of all cells tested. Responsive cells included both the cells that display the hyperpolarization-activated cation current (I-h) and cells that do not display I-h. An inhibitory effect of nicotine was never seen. Current-clamp recordings showed the nicotine-induced depolarization of a cell's membrane potential that could be sufficient to cause spontaneous firing. In voltage-clamp recordings, many cells showed nicotine-induced inward currents (18.3 +/- 3.2 pA, n = 6) that persisted during pharmacological blockade of synaptic transmission (e.g., zero [Ca2+](out) and 5 mM [Mg2+](out), n=6/8). Other two cells, however, showed increases in the frequency of excitatory postsynaptic currents (EPSCs), which were blocked by CNQX (n = 2/8). We analyzed miniature EPSCs (mEPSCs) recorded from cells that showed no inward currents but marked increases in the frequency of mEPSCs (0.8 +/- 0.2 to 4.8 +/- 1.7 Hz, n = 4) during nicotine application. Nicotine augmented mEPSC amplitude (n = 4); however, amplitude distribution was not significantly changed in two of four cells tested. We conclude that nicotinic receptors in the rat area postrema can excite cells via (1) a direct post- and/or extrasynaptic mechanism; and (2) an indirect enhancement of glutamate release. (C) 2004 Elsevier B.V. All rights reserved.

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  • The sensitivity of hyperpolarization-activated cation current (I-h) to propofol in rat area postrerna neurons Reviewed

    M Funahashi, Y Mitoh, R Matsuo

    BRAIN RESEARCH   1015 ( 1-2 )   198 - 201   2004.7

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    Area postrema neurons mediate various autonomic responses, including emesis. We examined the effects of propofol, a widely used anesthetic with antiemetic properties, on the hyperpolarization-activated cation current (I-h) in rat area postrema neurons using a slice patch-clamp technique. Although propofol suppressed 11, of area postrema neurons in a dose-dependent manner that was similar to what we observed for the hippocampal CA1 neurons, the IC50 for I-j, in area postrema neurons (38 muM) was more than six times less than that found for hippocampal CA1 neurons (235 muM). We conclude that rat area postrema neurons are exquisitely sensitive to propofol. Given that reductions of I-h are associated with decreased excitability in neurons, we believe that the known antiemetic effects of propofol anesthesia are at least partly a result of a direct action on area postrema neurons to lower their excitability. (C) 2004 Elsevier B.V. All rights reserved.

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  • Excitatory and inhibitory postsynaptic currents of the superior salivatory nucleus innervating the salivary glands and tongue in the rat Reviewed

    Y Mitoh, M Funahashi, M Kobashi, R Matsuo

    BRAIN RESEARCH   999 ( 1 )   62 - 72   2004.2

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    The excitatory and inhibitory synaptic inputs to parasympathetic preganglionic neurons in the superior salivatory (SS) nucleus were investigated in brain slices of neonatal (4-8 days old) rat using the whole-cell patch-clamp technique. The SS neurons innervating the submandibular and sublingual salivary glands and innervating the lingual artery in the anterior region of the tongue were identified by retrograde transport of a fluorescent tracer. Whole-cell currents were evoked by electrical stimulation of tissue surrounding the cell. These evoked postsynaptic currents were completely abolished by antagonists for N-methyl-D-aspartate (NMDA) glutamate, non-NMDA glutamate, gamma-aminobutyric acid type A (GABA(A)), and glycine receptors, suggesting that SS neurons receive glutamatergic excitatory, and GABAergic and glycinergic inhibitory synaptic inputs. In SS neurons for the salivary glands, the ratio of the NMDA component to the total excitatory postsynaptic current (EPSC) was larger than that of the non-NMDA component. This profile was reversed in the SS neurons for the tongue. In SS neurons for the salivary glands, the ratio of the GABA(A) component to the total IPSC was larger than the ratio of the glycine component to total inhibitory postsynaptic current (IPSC). The decay time constants of the GABAA component were slower than those for glycine. These characteristics of the excitatory and inhibitory inputs may be involved in determining the firing properties of the SS neurons innervating the salivary glands and the tongue. (C) 2004 Elsevier B.V. All rights reserved.

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  • Role of the hyperpolarization-activated cation current (I-h) in pacemaker activity in area postrema neurons of rat brain slices Reviewed

    M Funahashi, Y Mitoh, A Kohjitani, R Matsuo

    JOURNAL OF PHYSIOLOGY-LONDON   552 ( 1 )   135 - 148   2003.10

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    To clarify the functional properties of the hyperpolarization-activated cation current (I-h) as a pacemaker current in area postrema neurons, whole-cell recordings were made in visually identified cells in rat brain slices. The activation of I-h was identified in approximately 62% of area postrema neurons tested. The cells displaying I-h showed a depolarizing 'sag' in responses to hyperpolarizing current injection in current-clamp mode. The reversal potential for the I-h was -36 mV, and this was shown to depend on the external concentration of Na+ and K+ ions. Extracellular Cs+ ions (2 mm) and ZD7288 (100 am), a potent selective I-h channel antagonist, blocked I-h and induced a membrane potential hyperpolarization, suggesting the sustained activation of I-h near the resting potential and a contribution from I-h to membrane potential maintenance at more depolarized levels. In contrast, extracellular Ba2+ ions caused a depolarization of the membrane potential, suggesting the blockade of inward rectifier K+ currents. ZD7288 decreased the spontaneous discharge rate by prolonging the slow depolarization between two spikes, with minimal effect on the amplitude of the after-hyperpolarization or action potential waveforms. I-h stabilized the latency of rebound action potentials. I-h was weakly activated by external 8-bromoadenosine 3',5' cyclic monophosphate (I mm) or forskolin (50-100 mum), indicating that the I-h channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that I-h contributes to the subthreshold membrane and firing properties of rat area postrema. neurons and may regulate their resting membrane potential and firing patterns.

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  • Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on rat CA1 and CA3 pyramidal neurons Reviewed

    H Higuchi, M Funahashi, T Miyawaki, Y Mitoh, A Kohjitani, M Shimada, R Matsuo

    NEUROSCIENCE RESEARCH   45 ( 4 )   459 - 472   2003.4

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    Intracellular and field potential recordings were taken from the hippocampal CA1 and CA3 neurons in rat brain slices to investigate the effects of 2,6 di-isopropylphenol (propofol) on the neuronal excitability during GABA(A)-Cl channel blockade by picrotoxin (100 muM). Propofol produced a membrane hyperpolarization and an inhibition of the magnitude of the 'voltage sag' that was mediated by the activation of a hyperpolarization-activated inward current (I-H). Propofol (> 100 muM) decreased the spontaneous discharge rate of epileptiform burst responses in CA1 neurons up to 38+6% of the control level. Propofol also markedly reduced the duration of both spontaneous and evoked epileptiform burst responses. A propofol-induced decrease in the spontaneous discharge rate in CA3 neurons was coincident with that in CA1 neurons. The effects,of propofol on the membrane potential and spontaneous discharge rate but not on the duration of burst responses were duplicated by ZD7288 (potent selective antagonist for I-H channels), indicating that the blockade of I-H significantly contributes to reduction of cell's excitability. The present study suggests that various actions including suppressive effects on I-H contribute to the anesthetic and anti-convulsant properties of propofol. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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  • Mexiletine inhibits nonadrenergic noncholinergic lower oesophageal sphincter relaxation in rabbits Reviewed

    A Kohjitani, T Miyawaki, M Funahashi, Y Mitoh, R Matsuo, M Shimada

    EUROPEAN JOURNAL OF PHARMACOLOGY   465 ( 1-2 )   145 - 151   2003.3

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    Nonadrenergic noncholinergic (NANC) nerves are known to be nitrergic and to have an important role in the regulation of gastrointestinal motility and function. Cardiac antiarrhythmic therapy in humans is accompanied by a high incidence of gastrointestinal side-effects. We investigated the effect of mexiletine, a class Ib antiarrhythmic drug, on NANC lower oesophageal sphincter relaxation. Mexiletine concentration dependently inhibited the NANC relaxation induced by 30 mM KCl (EC50 = 4.4 x 10(-6) M); the production of 3',5'-cyclic guanosine monophosphate (cGMP) after KCl stimulation was concentration dependently decreased. The relaxation induced by the exogenous nitric oxide (NO) donor, diethylamine NONOate (10(-5) M), was not inhibited by mexiletine, and the cGMP production after diethylamine NONOate application was not altered. Mexiletine did not alter the activity of NO synthase. These findings suggest that mexiletine inhibits NANC relaxation via NO-cGMP pathway modulation, possibly by inhibiting myenteric nitrergic neurotransmission in the lower oesophageal sphincter in rabbits. (C) 2003 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0014-2999(03)01483-3

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  • Morphological study on the superior salivary nucleus innervating the submandibular and sublingual salivary glands and tongue in rats.(共著) Reviewed

    Matsuo R, Mitoh Y, Funahashi M, Kobashi M

    Dent Japan (Tokyo)   39   34 - 36   2003

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  • Electrophysiological properties of the rat area postrema neurons displaying both the transient outward current and the hyperpolarization-activated inward current Reviewed

    M Funahashi, Y Mitoh, R Matsuo

    BRAIN RESEARCH BULLETIN   58 ( 3 )   337 - 343   2002.7

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    We found coexistence of the transient outward potassium current (I-TO) and the hyperpolarization-activated inward current (I-H) in 26 of 82 area postrema neurons tested using the whole-cell patch-clamp technique in rat brain slices. Cells displaying both the I-TO and the I-H typically showed "voltage sag" and "rebound potentials" in response to hyperpolarizing current injection and repetitive firing with strong adaptation was seen with depolarizing current injection. When cells were held at membrane potentials more negative than the resting level (e.g., -85 mV), the afterhyperpolarization was enhanced. Voltage clamp recordings were performed to examine the characteristics of I-TO and I-H in and the contributions of these currents to the electroresponsiveness of area postrema cells. We show, in this study, the voltage-dependent properties of I-H and I-TO, and how these currents modulate the intrinsic membrane properties of area postrema cells. We discuss the functional significance of the specific subset of area postrema neurons whose cells have both I-H and I-TO channels. (C) 2002 Elsevier Science Inc. All rights reserved.

    DOI: 10.1016/S0361-9230(02)00798-0

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  • Two distinct types of transient outward currents in area postrema neurons in rat brain slices Reviewed

    M Funahashi, Y Mitoh, R Matsuo

    BRAIN RESEARCH   942 ( 1-2 )   31 - 45   2002.6

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    We investigated the electrophysiological properties of the area postrema neurons in acutely prepared rat brain slices using the whole-cell patch-clamp technique. Two different types of transient outward potassium current (I-to), fast and slow, were found in the area postrema. Both the decay time constant and rise time were significantly faster in the fast It. than in the slow I-to Both current-clamp and voltage-clamp recordings revealed that the activation of fast and slow I,. contributes to generation of the different spiking patterns, late spiking and interrupted spiking, respectively. The activation and inactivation of both I,. were strongly voltage-dependent. Curve fitting by the Boltzmann equation revealed no significant difference in the activation and inactivation curves for each I-to except that the slope factor of inactivation was larger for fast I-to. Both I-to were suppressed dose-dependently by application of 4-aminopyridine. Each spiking pattern was enhanced when cells were held at a more hyperpolarized membrane potential, i.e. a longer latency of the first spike or longer interspike interval between the first and second spikes. The voltage-dependent modulation of the spiking pattern was consistent with the voltage-dependent activation of I-to. The present study shows significant subdivisions of the area postrema neurons distinguished by a difference in the kinetics of I-to and spiking patterns. We discuss the role of I,, as the ionic current underlying neuronal excitability. (C) 2002 Elsevier Science B.V. All rights reserved.

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  • Effects of amiloride on gustatory neural responses to salts in the frog Reviewed

    Y Kitada, K Okuda-Akabane, Y Mitoh

    CHEMICAL SENSES   26 ( 9 )   1203 - 1210   2001.11

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    In frogs, the glossopharyngeal nerve (GL) innervates taste receptors or almost the entire tongue. The mandibular branch (MBF) and palatine branch (PN) of the facial nerve innervate taste receptors on a very small area at the base of the tongue and on the palate, respectively, In the present study, effects of amiloride, an epithelial sodium channel blocker, on the toric responses of the GL, MBF and PN in frogs to NaCl, LiCl, KCl and CaCl2 were investigated, In three nerves, amiloride at 0.5 mM, a relatively high concentration, did not affect the responses to 0.15 (concentration just above threshold)-0.5 M NaCl, 0.5 M LiCl and 0.3 M KCl, whereas it almost completely inhibited the response to 1.0 mM CaCl2. Amiloride may exert an inhibitory action on the response to CaCl2 by a competitive antagonism between Ca2+ and a monovalent cation of amiloride, because the response to Ca2+ is competitively inhibited by other cations such as Na+ and Mg2+. The lack of inhibitory effect of amiloride on the responses in the GL, MBF and PN to NaCl suggests that amiloride-sensitive sodium channels in the apical membrane of taste receptor cells are not involved in sodium taste transduction in frogs.

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  • Intravenous anesthetics inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation via nitric oxide-cyclic guanosine monophosphate pathway modulation in rabbits Reviewed

    A Kohjitani, T Miyawaki, M Funahashi, Y Mitoh, R Matsuo, M Shimada

    ANESTHESIOLOGY   95 ( 1 )   176 - 183   2001.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Background: Nonadrenergic noncholinergic (NANC) nerves have important roles in the regulation of the lower esophageal sphincter (LES) motility and function, The effects of thiopental, ketamine, and midazolam on NANC LES relaxation were investigated.
    Methods: The isometric tension of circular muscle strips from Japanese White rabbits was examined. The NANC relaxation was Induced by KCl (30 mM) in the presence of atropine (3 x 10(-6) M) and guanethidine (3 x 10(-6) M), The modifications of the NANC and sodium nitroprusside (SNP; 10(-6) M)-induced relaxation by the anesthetics were examined. The content of 3 ' ,5 ' -cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay.
    Results: The KCl-induced relaxation was abolished by pretreating with tetrodotoxin (10(-6) M). The NANC relaxation was inhibited in the presence of NG-nitro-L-arginine (L-NNA; 3 x 10(-5) M), methylene blue (10(-6) M), apamin (10(-7) M), and gilbenclamide (10(-5) M). The SNP-induced relaxation was inhibited by methylene blue but was not affected by tetrodotoxin, L-MYA, apamin, or glibenclamide, Ketamine (EC50 = 8.8 x 10(-5) M) and midazolam (EC50 = 4.8 x 10(-6) M) suppressed the NANC response in a concentration-dependent manner, leaving SNP-induced response unchanged Thiopental altered neither of the relaxations. cGMP content was decreased in the presence of ketamine and midazolam.
    Conclusion: The NANC relaxation was mediated by nitric oxide and by low-conductance calcium- and adenosine triphosphate-sensitive potassium channels of smooth muscle. The modulation of the nitric oxide-GMP pathway was related at least in part, to the inhibitory actions of ketamine and midazolam on the NANC LES relaxation.

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  • Role of parabrachial nucleus in submandibular salivary secretion induced by bitter taste stimulation in rats Reviewed

    R Matsuo, Y Yamauchi, M Kobashi, M Funahashi, Y Mitoh, A Adachi

    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL   88 ( 1-2 )   61 - 73   2001.4

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    When rats lick a bitter taste solution such as quinine-hydrochloride, they secrete profuse amounts of saliva. The salivation has a higher flow rate than that induced by other qualities of taste stimulation: sweet, salty, and sour, The present study is aimed to clarify the neural mechanism of the quinine-evoked salivation by means of behavioral, neuroanatomical, and electrophysiological experiments. Behaviorally, submandibular salivary secretion and rejection behavior (gaping) were observed in normal rats. as well as in rats chronically decerebrated at the precollicular level. In chronically decerebrate rats, these quinine-evoked reactions were strongly suppressed by destruction of the medial part of the parabrachial nucleus, including the so-called taste area, and ventral part of the parabrachial nucleus, including the pontine reticular formation. Neuroanatomical study using a retrograde tracer. Fluoro-gold, revealed that the neurons sending their axons to the superior salivatory nucleus, parasympathetic secretory center, were located mainly in the pontine reticular formation ventral to the parabrachial nucleus. not in the parabrachial taste area. Extracellular neural activity was recorded from the parabrachial region in decerebrate rats, and responsiveness to taste stimulation, jaw movements, and electrical stimulation of the superior salivatory nucleus was examined. Neurons responsive to both taste stimulation and antidromic stimulation of the superior salivatory nucleus were Found in the pontine reticular formation ventral to the parabrachial nucleus, which responded well to quinine and HCl taste stimuli. Neurons in the parabrachial taste area could respond to four qualities of taste stimulation, but not to antidromic stimulation of the salivary center. These results suggest that aversive taste information from the parabrachial taste area reaches the salivary secretory center via the reticular formation ventral to the parabrachial nucleus. (C) 2001 Elsevier Science B.V. All rights reserved.

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  • Salt taste responses of the IXth nerve in Sprague-Dawley rats: Lack of sensitivity to amiloride Reviewed

    Y Kitada, Y Mitoh, DL Hill

    PHYSIOLOGY & BEHAVIOR   63 ( 5 )   945 - 949   1998.3

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    To explore characteristics of the salt taste function of taste receptor cells located on the posterior tongue, we recorded electrophysiological responses from the whole glossopharyngeal nerve in Sprague-Dawley (SD) rats. For all salts, relative response magnitudes increased with increased stimulus concentrations (0.2-2.0 M) of NH4+, K+, and Na+ salts. The order of effectiveness of stimulation for Cl- salts was NH4Cl > KCl > NaCl. For sodium salts, relative response magnitudes were anion dependent. Sodium salts with small anions (NaCl, NaSCN, and NaNO3) had a much stronger stimulating effect than sodium salts with large anion groups (Na2SO4, C2H3O2Na, and C6H11O7Na). The responses of the glossopharyngeal nerve to the Na+ salts of NaCl, C2H3O2Na, and C6H11O7Na were not inhibited by the lingual application of the epithelial sodium transport blocker amiloride. This is in contrast to large amiloride sensitivity of the chorda tympani nerve. Amiloride also failed to inhibit the responses to K+ salts (KCl and KC2H3O2) and to NH4Cl. These results demonstrate that taste receptors innervated by the glossopharyngeal nerve in SD rats lack amiloride sensitivity as observed in the glossopharyngeal nerve of spontaneously hypertensive and Wistar-Kyoto rats. Furthermore, the difference between the small-anion group and the large-anion group of Na+ salts in their effectiveness to produce responses in the glossopharyngeal nerve parallels the effects noted for the anion dependence in the portion of the taste response resistant to amiloride in the chorda tympani nerve. Sodium salts with the smaller anion produced the larger responses in both glossopharyngeal and chorda tympani nerves after amiloride. (C) 1998 Elsevier Science Inc.

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  • Effects of a bite-raising splint on the duration of the chewing cycle and the EMG activities of masticatory muscles during chewing in freely moving rabbits Reviewed

    Y Matsuka, Y Kitada, Y Mitoh, A Adachi, A Yamashita

    JOURNAL OF ORAL REHABILITATION   25 ( 2 )   159 - 165   1998.2

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    Metal bite-raising splints of 0.5 mm thickness were attached to the upper molar teeth on both sides of the jaw in rabbits. The effects of these splints on masticatory behaviour during the chewing of soft food (bread) by freely moving rabbits were investigated. We recorded electromyograms (EMGs) of the masseter and digastric muscles. The animals exhibited prolongation of the chewing cycle, decreased EMG activity of the masseter muscle and increased EMG activity of the digastric muscle during chewing after introduction of the bite-raising splints. The effects of the splints on the activities of masticatory muscles were abolished by bilateral sectioning of the maxillary and inferior alveolar nerves. It seems likely that afferents from oral sensory receptors were responsible for the changes in masticatory behaviour after the introduction of the occlusal splint.

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  • Enhancing effect of nickel ions on the response to magnesium ions of single fibers of the frog glossopharyngeal nerve: Competitive inhibition by calcium ions of the nickel-enhanced response to magnesium ions Reviewed

    Y Kitada, Y Mitoh

    CHEMICAL SENSES   22 ( 6 )   613 - 622   1997.12

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    Single fibers of the frog glossopharyngeal nerve respond to MgCl2 at concentrations exceeding 10 mM. NICl2 at 1 mM enhanced the Mg2+ response. CaCl2 at 0.5-2 mM induced an inhibition of the Ni2+-enhanced response to Mg2+ ions. A quantitative explanation for these results is provided by the hypothesis that Ni2+ ions secondarily affect a magnesium receptor (designated X*Mg) that is responsible for the Mg2+ response and that Ca2+ ions inhibit the Ni2+-enhanced response to Mg2+ ions by competing with Mg2+ ions for X*Mg Double-reciprocal plots of the experimental data indicate that Ni2+ ions dd not affect the affinities of X*Mg for both Mg2+ ions (agonist) and Ca2+ ions (competitive antagonist) appreciably, and that Ni2+ ions at 1 mM enhanced the maximal response to Mg2+ ions by 270%. It appears that a magnesium receptor interacts with an Ni2+-binding element that is affected by Ni2+ ions and, thus, Ni2+ ions can induce an enhancement of the Mg2+ response.

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  • A quantitative study of the enhancing effect of nickel ions on the taste response to sodium ions of single fibers of the frog glossopharyngeal nerve: Competitive inhibition by calcium ions of the nickel-enhanced response to sodium ions Reviewed

    Y Kitada, Y Mitoh

    CHEMICAL SENSES   21 ( 1 )   65 - 73   1996.2

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    Single water fibers of the frog glossopharyngeal nerve respond to relatively high concentrations of NaCl (>80 mM). NiCl2 at 1 mM enhanced the Na+ response and reduced the threshold concentration for NaCl to 20 mM. CaCl2 at 0.5-1 mM induced an inhibition of the Ni2+-enhanced response to Na+ ions. A quantitative explanations for these results is provided by the hypothesis that Ni2+ ions secondarily affect a sodium receptor or channel (designated X(Na)*) that is responsible for the Na+ response and that Ca2+ ions inhibit the Ni2+-enhanced response to Na+ ions by competing with Na+ ions for X(Na)*. Double-reciprocal plots of the experimental data indicate that the affinity of X(Na)*, for both Na+ ions (agonist) and Ca2+ ions (competitive antagonist) in the presence of 1 mM NiCl2 was five times higher than the previously reported values obtained in the absence of NiCl2 (Kitada, 1991). Ni2+ ions at 1 mM enhanced the maximal response to Na+ ions by 190%. It appears that a sodium receptor (or channel) interacts with a Ni2+-binding element that is affected by Ni2+ ions and, thus, Ni2+ ions can induce both an increase in the affinity of the sodium receptor for the respective cations and an enhancement of the Na+ response.

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  • Influence of occlusal changes on masticatory behavior in rabbits Reviewed

    Y Matsuka, Y Kitada, N Jitsunari, Y Mitoh, H Yatani, A Yamashita

    BRAIN AND ORAL FUNCTIONS   1079   339 - 342   1995

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    Language:English   Publishing type:Research paper (international conference proceedings)   Publisher:ELSEVIER SCIENCE PUBL B V  

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  • DEVELOPMENT OF A SENSITIVE ENZYME-IMMUNOASSAY FOR OPC-7251 - A NOVEL ANTIMICROBIAL AGENT FOR PERCUTANEOUS APPLICATION Reviewed

    N MUTO, Y MITOH, YAMAMOTO, I

    JOURNAL OF IMMUNOASSAY   11   1 - 6   1990.11

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  • ANTISCORBUTIC ACTIVITY OF L-ASCORBIC-ACID 2-GLUCOSIDE AND ITS AVAILABILITY AS A VITAMIN-C SUPPLEMENT IN NORMAL RATS AND GUINEA-PIGS Reviewed

    YAMAMOTO, I, S SUGA, Y MITOH, M TANAKA, N MUTO

    JOURNAL OF PHARMACOBIO-DYNAMICS   13 ( 11 )   688 - 695   1990.11

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    Bioavailability of a newly-synthesized and chemically-stable 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) as a vitamin C supplement was investigated in rats and guinea pigs. Oral administration of AA-2G to the animals resulted in an increase of serum ascorbic acid (AA) levels. However, in these sera the intact form was not detectable by the high performance liquid chromatography (HPLC) method, indicating its hydrolysis through the process of absorption. After an intravenous injection of AA-2G, the intact form diminished rapidly from the serum, followed by prolonged and marked elevation of serum AA levels. Various tissue homogenates from rats and guinea pigs were examined for their releasing activity of AA from AA-2G. High activity was observed in kidney, small intestine and serum of rats and in small intestine and kidney of guinea pigs. These hydrolytic activities were completely inhibited by castanospermine, a specific alpha-glucosidase inhibitor, suggesting the participation of alpha-glucosidase in the in vivo hydrolysis of AA-2G. AA-2G was found to exhibit obvious therapeutic effect in scorbutic guinea pigs by its repeated oral administrations. These results indicate that AA-2G is a readily available source of vitamin C activity in vivo.

    DOI: 10.1248/bpb1978.13.688

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Books

  • 平成30-令和2年度科学研究費補助金(基盤研究C)成果報告書

    美藤純弘( Role: Sole author)

    日本学術振興会  2021.5 

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    Language:Japanese

  • 平成30-令和2年度科学研究費補助金(基盤研究C)成果報告書

    美藤純弘( Role: Sole author)

    日本学術振興会  2021.5 

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  • A study for role of the feeding center in submandibular and sublingual salivary secretion

    Yoshihiro Mitoh( Role: Sole author)

    Japan Society for the Promotion of Science  2016 

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  • 平成21-23年度科学研究費補助金(基盤研究C)成果報告書

    美藤純弘( Role: Sole author ,  摂食関連ペプチドによる上唾液核ニューロン活動の調節機構に関する研究)

    日本学術振興会  2011 

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  • 平成19-20年度科学研究費補助金(基盤研究C)成果報告書

    美藤純弘( Role: Sole author ,  抑制系を指標にした口腔機能の生後発育の電気生理学的解析.)

    日本学術振興会  2009 

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  • 薬剤師・MR・コメディカルのための救急医療マニュアル

    *美藤純弘 他(6.3 ハチ毒アナフィラキシー・ショックとエピペンの取り扱い.)

    エルゼピア・ジャパン,東京  2007 

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    Responsible for pages:82-88  

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  • 生物学に関する試験研究論叢(第二十二集)

    *美藤純弘、根岸友恵、阿保達彦、斉藤健司、津田誠、上村一雄、畑中唯史、稲垣賢二、岸本晃治、前川賢治、河井まりこ、森宏樹、大塚文男、(口腔機能の生後発育に関する神経生理学的研究ー抑制性ニューロンの機能を指標にした解析ー.)

    財団法人 両備てい園記念財団  2007 

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    Responsible for pages:1-8  

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  • 平成17-18年度科学研究費補助金(基盤研究C)成果報告書

    *美藤純弘( Role: Sole author ,  抑制系を指標にした口腔機能の生後発育の電気生理学的解析.)

    日本学術振興会  2007 

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  • Neurobiology of Mastication-from Molecular to Systems Approach

    Kitada Y, Okuda-Akabane K, Kawarada K, Mitoh Y( Role: Joint author ,  Effect of amiloride on the taste responses of the frog glossopharyngeal nerve to Ca,Mg and Na salts.)

    Elsevier Science B.V.  1999 

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  • Hepatic osmosensors and their role in fluid homeostasis.(共著)

    ( Role: Joint author)

    John Libbey & Company  1996 

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    Responsible for pages:ReaD移行データ日付 : 1996   Language:English

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  • Influence of occlusal changes on masticatory behavior in rabbits.(共著)

    ( Role: Joint author)

    Elsevier Science B.V.  1995 

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    Responsible for pages:339-342   Language:English

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MISC

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Presentations

  • Enantiomers of organic acids are identified by the preference taste receptors Tas1R2/Tas1R3 or Tas1R1/Tas1R3

    Yuko Yamase, Hai Huang, Yoshihiro Mitoh, Kengo Horie, Ryusuke Yoshida

    The 20th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception  2023.11.26 

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    Event date: 2023.11.25 - 2023.11.26

    Language:English   Presentation type:Poster presentation  

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  • SNAP-25 contributes to the maintenance of Type III taste receptor cells

    Kengo Horie, Hai Huang, Kuanyu Wang, Yu Zuo, Keiko Yasumatsu, Yuzo Ninomiya, Yoshihiro Mitoh, Ryusuke Yoshida

    The 20th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception  2023.11.26 

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    Event date: 2023.11.25 - 2023.11.26

    Language:English   Presentation type:Oral presentation (general)  

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  • Ccn3 expression in the murine taste bud does not confer essential roles in taste perception

    Kuanyu Wang, Yoshihiro Mitoh, Kengo Horie, Ryusuke Yoshida

    The 20th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception  2023.11.26 

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    Event date: 2023.11.25 - 2023.11.26

    Language:English   Presentation type:Poster presentation  

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  • Analysis of mice lacking synapses in taste buds

    Ryusuke Yoshida, Kengo Horie, Yoshihiro Mitoh

    The 65th Annual Meeting of Japanese Association for Oral Biology  2023.9.18 

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    Event date: 2023.9.16 - 2023.9.18

    Language:English   Presentation type:Poster presentation  

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  • Effects of dopamine on the superior salivatory nucleus neurons innervating the salivary glands in rats

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Kengo Horie, Hiroyuki Ichikawa, Ryusuke Yoshida

    The 65th Annual Meeting of Japanese Association for Oral Biology  2023.9.18 

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    Event date: 2023.9.16 - 2023.9.18

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  • 唾液緩衝能が味覚に及ぼす影響について

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2023.9.13 

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    Event date: 2023.9.11 - 2023.9.13

    Language:English   Presentation type:Poster presentation  

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  • CN3 expression in the murine taste bud does not confer essential roles in taste perception

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2023.9.13 

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    Event date: 2023.9.11 - 2023.9.13

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  • 甘味・うま味受容体が有機酸の光学異性体の識別に関与している

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2023.9.12 

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    Event date: 2023.9.11 - 2023.9.13

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  • 糖刺激による頭相インスリン分泌の誘発

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2023.9.12 

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    Event date: 2023.9.11 - 2023.9.13

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  • Expression of taste related genes in the central chemoreceptor area of mouse brain

    Yuri Namba, Yoshihiro Mitoh, Suzuka Yoshida, Yohei Takeshita, Junichi Asaumi, Ryusuke Yoshida

    The 46th Annual Meeting of the Japan Neuroscience Society  2023.8.2 

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    Event date: 2023.8.1 - 2023.8.4

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  • Elucidation of the mechanism of the gustatory salivary reflex using mice: c-Fos expression in the central nervous system.

    Adachi Reimi, Mitoh Yoshihiro, Yoshida Ryusuke

    The 100th Annual Meeting of the Physiological Society of Japan  2023.3.14 

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    Event date: 2023.3.14 - 2023.3.16

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  • Relationship between salivary buffering capacity and taste sensitivity in humans

    Aiko Hyodo, Yoshihiro Mitoh, Ryusuke Yoshida

    The 100th Annual Meeting of the Physiological Society of Japan  2023.3.14 

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    Event date: 2023.3.14 - 2023.3.16

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  • 発酵乳成分におけるマウスの味覚応答の解析

    山瀬裕子, 黄海, 美藤純弘, 江草正彦, 宮脇卓也, 吉田竜介

    第43回岡山歯学会  2022.12.11 

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    Event date: 2022.12.11

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 唾液腺支配の上唾液核ニューロンに対するドーパミンの影響

    美藤純弘、佐藤匡、矢島健大、小橋基、市川博之、吉田竜介

    第 55 回 日本栄養•食糧学会 中国•四国支部大会  2022.10.30 

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    Event date: 2022.10.29 - 2022.10.30

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Excitatory effects of dopamine on the superior salivatory nucleus neurons innervating the rat submandibular and sublingual salivary glands

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Motoi Kobashi, Hiroyuki Ichikawa, Ryusuke Yoshida

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2022.8.24 

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    Event date: 2022.8.22 - 2022.8.24

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  • Behavioral analysis of taste responses to ingredients in fermented milk in mice

    Yuko Yamase, Huang Hai, Yoshihiro Mitoh, Masahiko Egusa, Takuya Miyawaki, Ryusuke Yoshida

    The 56th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2022.8.22 

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    Event date: 2022.8.22 - 2022.8.24

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  • Immunohistochemical study on the distribution of orexinergic nerve fibers and receptors in the superior salivatory nucleus

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Hiroyuki Ichikawa, Motoi Kobashi, Ryusuke Yoshida

    The 98th Annual Meeting of the Physiological Society of Japan  2021.3.30 

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    Event date: 2021.3.28 - 2021.3.30

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  • Mutual interaction of orexin-A and glucagon-like peptide-1 on reflex swallowing in rats

    Motoi Kobashi, Masako Fujita, Yoshihiro Mitoh

    The 62nd Annual Meeting of Japanese Association for Oral Biology  2020.9.11 

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    Event date: 2020.9.11 - 2020.10.9

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  • オレキシンは顎下腺・舌下腺支配の副交感神経節前ニューロンを興奮させる

    美藤純弘, 佐藤 匡, 矢島健太, 藤田雅子, 小橋基, 市川博之, 吉田竜介

    第74回日本栄養・食糧学会大会  2020.5.16 

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    Event date: 2020.5.15 - 2020.5.17

    Language:Japanese   Presentation type:Poster presentation  

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  • Effects of appetite-boosting peptides on the superior salivatory nucleus neurons in rats

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Masako Fujita, Hiroyuki Ichikawa, Motoi Kobashi, Ryusuke Yoshida

    The 97th Annual Meeting of the Physiological Society of Japan  2020.3.19 

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    Event date: 2020.3.17 - 2020.3.19

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  • 上唾液核ニューロンの摂食亢進ペプチドの影響

    美藤純弘, 佐藤匡, 矢島健太, 藤田雅子, 小橋基, 市川博之, 吉田竜介

    第40回岡山歯学会  2019.12.15 

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    Event date: 2019.12.15

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Effects of appetite-boosting peptides on the superior salivatory nucleus neurons innervating the salivary glands in rats

    Yoshihiro Mitoh, Tadasu Sato, Masako Fujita, Motoi Kobashi, Hiroyuki Ichikawa, Ryusuke Yoshida

    The 61st Annual Meeting of Japanese Association for Oral Biology  2019.10.14 

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    Event date: 2019.10.12 - 2019.10.14

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  • Effects of appetite-boosting peptides on parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands in rats.

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Masako Fujita, Motoi Kobashi, Hiroyuki Ichikawa, Ryusuke Yoshida

    The 53th Annual Meeting of the Japanese Association for the Study of Taste and Smell  2019.9 

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    Event date: 2019.9.17 - 2019.9.19

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  • Effects of feeding-promoting peptides on excitability of the superior salivatory nucleus neurons

    Yoshihiro Mitoh, Tadasu Sato, Masako Fujita, Hiroyuki Ichikawa, Motoi Kobashi, Ryusuke Yoshida

    9th FAOPS Congress(FAOPS2019)  2019.3.29 

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    Event date: 2019.3.28 - 2019.3.30

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  • Mutual interaction of orexin-A and glucagon-like peptide-1 on reflex swallowing in anesthetized rats

    Motoi Kobashi, Yuichi Shimatani, Masako Fujita, Yoshihiro Mitoh, Ryuji Matsuo

    9th FAOPS Congress(FAOPS2019)  2019.3.28 

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    Event date: 2019.3.28 - 2019.3.30

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  • Effects of peptides promoting food intake on the superior salivatory nucleus neurons innervating the submandibular and sublingual salivary glands

    Yoshihiro Mitoh, Tadasu Sato, MasakoFujita, Hiroyuki Ichikawa, Motoi Kobashi

    The 60rd Annual Meeting of Japanese Association for Oral Biology  2018.9.18 

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    Event date: 2018.9.5 - 2018.9.7

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  • GLP-1 はオレキシンA による嚥下減弱作用を抑制する

    小橋 基, 島谷 祐一, 藤田 雅子, 美藤 純弘, 松尾 龍二

    第95回日本生理学会大会  2018.3.28 

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    Event date: 2018.3.28 - 2018.3.30

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  • Orexin-A diminishes the suppressive effect of GLP-1 on the reflex swallowing

    2017 

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  • オレキシン A は GLP-1 による嚥下減弱作用を抑制する

    第94回日本生理学会大会  2017 

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  • Orexins excite parasympathetic preganglionic neurons in the superior salivatory nucleus innervating the salivary glands.

    17th International Symposium on Olfaction and Taste (ISOT2016)  2016 

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  • GLP-1 suppresses reflex swallowing via the medial part of nucleus tractus solitarius

    2015 

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  • GLP-1は孤束核内側部を介して反射性嚥下を抑制する

    第92回日本生理学会大会  2015 

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  • GLP-1 の嚥下反射減弱作用に及ぼすオレキシン A の効果

    日本味と匂学会第49回大会  2015 

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  • オレキシンはラット顎下唾液腺を支配する上唾液核ニューロンを興奮させる

    第56回歯科基礎医学会学術大会・総会  2014 

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  • GLP-1 中枢投与による嚥下反射におよぼす作用

    第91回日本生理学会大会  2014 

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  • Effects of orexins on parasympathetic preganglionic neurons in the superior salivatory nucleus innervating the salivary glands.

    2014 

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  • Identification of the effective site of GLP-1 to suppress reflex swallowing.

    2014 

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  • 顎下腺・舌下腺を支配する上唾液核ニューロン活動の摂食中枢による調節

    第35回岡山歯学会総会・学術集会  2014 

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  • 渋味溶液の舌刺激による舌神経と鼓索神経の応答と温度覚との関連

    第56回歯科基礎医学会学術大会・総会  2014 

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  • GLP-1 中枢投与による反射性嚥下抑制を惹起する部位の同定

    日本味と匂学会第48回大会  2014 

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  • 上唾液核における唾液腺支配の副交感神経節前ニューロンに対するオレキシンの影響

    第91回日本生理学会大会  2014 

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  • GLP-1中枢投与による反射性嚥下修飾作用

    日本味と匂学会第46回大会  2013 

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  • ラット顎下腺・舌下腺を支配する上唾液核ニューロンに対するオレキシンの興奮作用

    第55回歯科基礎医学会学術大会・総会  2013 

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  • Developmental Switch of GABA Action in Superior Salivatory Nucleus Neurons.

    第3回岡山医療教育研究シンポジウム  2013 

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  • ラット中枢 GLP-1 の反射性嚥下におよぼす作用

    第55回歯科基礎医学会学術大会・総会  2013 

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  • タンニン酸の舌刺激に対するラット舌神経と鼓索 神経の応答

    第55回歯科基礎医学会学術大会・総会  2013 

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  • オレキシン-A は孤束核交連部のオレキシン 1 受容体を介して嚥下反射を抑制する

    第90回日本生理学会大会  2013 

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  • オレキシン-Aによる反射性嚥下抑制を惹起する中枢作用部位の検討

    日本味と匂学会第46回大会  2012 

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  • 嚥下反射抑制におよぼすオレキシン A 作用部位の検討

    第89回日本生理学会  2012 

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  • ラット大脳皮質の電気刺激で誘発されるリズミカルな顎運動と唾液分泌の関連

    第54回歯科基礎医学会学術大会・総会  2012 

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  • ラット中枢オレキシンによる反射性嚥下の抑制

    第88回日本生理学会大会 (震災のため中止、誌上開催)  2011 

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  • オレキシンはラット顎下腺・舌下腺を支配する上唾液核ニューロンの興奮性を促進する

    第53回歯科基礎医学会学術大会・総会  2011 

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  • オレキシン中枢投与による嚥下反射の抑制

    日本味と匂学会第45回大会  2011 

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  • オレキシン中枢投与による反射性嚥下の抑制

    第53回歯科基礎医学会学術大会・総会  2011 

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  • ラット大脳皮質咀嚼野の電気刺激が誘発するリズミカルな顎運動と唾液分泌の関連

    第53回歯科基礎医学会学術大会・総会  2011 

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  • ラット上唾液核へのGABA作動性抑制性入力に関する免疫組織化学的研究

    第52回歯科基礎医学会学術大会・総会  2010 

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  • Central ghrelin induces gastric relaxation of the proximal stomach via the caudal dorsal vagal complex in the rat

    The 36th Congress of the International Union of Physiological Sciences  2009 

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  • Cevimeline enhances the excitability in the rat superior salivatory nucleus neurons

    The 36th Congress of the International Union of Physiological Sciences  2009 

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  • Cevimeline enhances the excitability in the rat superior salivatory nucleus

    The 11th International Symposium on Exocrine Secretion Tokushima 09-Exocrine Secretion-Mechanism and Disease  2009 

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  • Postnatal development of inhibitory synaptic transmission to the superior salivatory neurons in rats

    The 11th International Symposium on Exocrine Secretion Tokushima 09-Exocrine Secretion-Mechanism and Disease  2009 

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  • 中枢摂食亢進ペプチドによる麻酔下ラット胃近位部の弛緩応答

    第7回せとうち消化管運動研究会  2009 

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  • Immunohistochemical study on the Distribution and origin of GABAergic nerve terminals in the superior salivatory nucleus

    The 11th International Symposium on Exocrine Secretion Tokushima 09-Exocrine Secretion-Mechanism and Disease  2009 

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  • GABAergic nerve terminals in the superior salivatory nucleus; immunohistochemical and retrograde tracing study

    The 36th Congress of the International Union of Physiological Sciences  2009 

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  • ラット上唾液核における抑制性受容体と抑制性ニューロンの中枢分布に関する免疫組織化学的研究

    第51回 歯科基礎医学会学術大会・総会  2009 

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  • Central ghrelin induces proximal stomach relaxation and inhibits reflex swallowing in the anaesthetized rats

    グレリン国際シンポジウム2009  2009 

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  • ラット上唾液核ニューロンに対するセビメリンの興奮性作用に関する電気生理学的および免疫組織化学的解析

    第51回 歯科基礎医学会学術大会・総会  2009 

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  • ラット上唾液核に投射するGABA作動性ニューロンの分布

    第85回日本生理学会大会  2008 

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  • セビメリンはラット上唾液核ニューロンの興奮性を促進する

    第50回 歯科基礎医学会  2008 

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  • 中枢摂食亢進ペプチドによる嚥下の調節作用

    「咀嚼・嚥下」研究発表会 咀嚼・嚥下の生理学的メカニズム、神経性調節の解明  2008 

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  • ラット上唾液核に投射する抑制性ニューロンの分布

    第50回 歯科基礎医学会  2008 

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  • ラット脳スライスにおける最後野ニューロン活動に対するムスカリン受容体活性化による興奮性および抑制性効果

    第85回日本生理学会大会  2008 

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  • プレートの厚みおよび噛みしめ様式がヒトのヒラメ筋H反射に及ぼす影響

    第85回日本生理学会大会  2008 

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  • ラット上唾液核に投射するGABA作動性ニューロンの分布

    第85回日本生理学会大会  2007 

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  • ラット中枢グレリンによる反射性嚥下の調節作用

    第49回 歯科基礎医学会  2007 

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  • ラット脳スライス標本における延髄最後野ニューロンのセピメリンによる興奮性応答

    第49回 歯科基礎医学会  2007 

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  • ラット顎下腺の自律神経中を走行する求心性神経の応答特性

    第49回 歯科基礎医学会  2007 

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  • 上喉頭神経由来の反射性嚥下におよぼす中枢グレリンの調節作用

    日本味と匂学会第41回大会  2007 

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  • 最後野におけるP2X受容体の局在とその機能

    第49回歯科基礎医学会サテライトシンポジウムⅧ 「口腔機能の中枢制御-電気生理学的アプローチ-」  2007 

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  • 中枢摂食亢進ペプチドによるラット胃近位部の弛緩応答

    第49回日本平滑筋学会総会  2007 

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  • ラット脳スライスにおける最後野ニューロン活動に対するムスカリン受容体活性化による興奮性および抑制性効果

    第85回日本生理学会大会  2007 

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  • プレートの厚みおよび噛みしめ様式がヒトのヒラメ筋H反射に及ぼす影響

    第85回日本生理学会大会  2007 

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  • Electrophysiological study of the inhibitory inputs from the forebrain and brainstem to the superior salivatory nucleus in rats.

    3rd International symposium on salivary glands in honor of Niels Stensen.  2006 

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  • ラット上唾液核細胞における抑制性シナプス伝達の発達

    第83回日本生理学会大会  2006 

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  • ニューロペプチドYの胃近位部弛緩におよぼす中枢性作用

    第83回日本生理学会大会  2006 

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  • Electrophysiological study on the descending excitatory synaptic inputs to the superior salivatory nucleus in the rat.

    3rd International symposium on salivary glands in honor of Niels Stensen.  2006 

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  • ラット脳スライス中の孤束膠様核ニューロンの形態学的特徴と化学感受性

    第83回日本生理学会大会  2006 

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  • 圧刺激に反応するラット顎下腺からの求心性情報の電気生理学的解析

    第83回日本生理学会大会  2006 

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  • 種々の食物摂取によるラット顎下腺唾液分泌の測定

    第83回日本生理学会大会  2006 

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  • ラット最高野ニューロンにおける細胞外ATPの膜電位および自発発火に対する効果

    第83回日本生理学会大会  2006 

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  • The inhibitory synaptic inputs to the superior salivatory nucleus

    Japanese Association for Dental Research 53rd Annual Meeting  2005 

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  • Modulation of area postrema neuronal excitability via P2X purinoceptors in rat brain slices.

    第35回北米神経科学会  2005 

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  • Functional interaction between neurons in the area postrema and in the nucleus gelatinosus solitarius.

    第35回北米神経科学会  2005 

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  • The excitatory inputs to the superior salivatory neurons

    Japanese Association for Dental Research 53rd Annual Meeting  2005 

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  • ラット上唾液核細胞に対する下行性の興奮性および抑制性入力に関する電気生理学的研究

    平成16年度生理研研究会「唾液分泌機構解明に向けての戦略的展開」  2005 

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  • 自律系ニューロンのおもしろさ:延髄最後野単一ニューロンの形態および機能の多様性

    第82回日本生理学会大会  2005 

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  • ラット顎下腺に分布する感覚神経の入力経路に関する組織化学的研究

    第25回岡山歯学会総会  2005 

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  • 飼料摂食時のラット顎下腺唾液分泌量と咀嚼筋活動の分析

    第47回 歯科基礎医学会  2005 

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  • 最後野におけるプリン受容体(P2X)による神経活動の修飾

    第47回 歯科基礎医学会  2005 

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  • 孤束膠様核単一ニューロンの形態的特徴,膜特性および化学感受性

    第47回 歯科基礎医学会  2005 

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  • 舌および顎下腺・舌下腺を支配するラット上唾液核細胞における抑制性シナプス伝達の生後発達

    第47回 歯科基礎医学会  2005 

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  • 迷走神経複合核のニューロペプチドY-Y1受容体を介した胃近位部弛緩の解析

    第47回 歯科基礎医学会  2005 

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  • ラット最高野ニューロンの機能と形態

    第85回日本生理学会北海道地方会  2005 

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  • ニューロペプチドY-Y1受容体を介した胃近位部の食物受け入れ応答

    日本味と匂学会第39回大会  2005 

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  • ラット上唾液核ニューロンに対する下行性の興奮性シナプス入力に関する電気生理学的検討

    第82回日本生理学会大会  2005 

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  • ラット上唾液核細胞に対する下行性抑制性シナプス入力に関する電気生理学的解析

    第82回日本生理学会大会  2005 

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  • 脳スライス標本における最後野ニューロンのATP受容体を介する興奮性の修飾

    第82回日本生理学会大会  2005 

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  • ラット顎下腺求心性神経の経路に関する組織化学的研究

    第82回日本生理学会大会  2005 

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  • ラット上最高野ニューロンの電気生理学的および形態学的特徴

    第81回日本生理学会大会  2004 

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  • 口腔領域の刺激によるラット顎下腺唾液分泌の神経生理学的研究

    第81回日本生理学会大会  2004 

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  • ラット上唾液核細胞のシナプス入力に関する電気生理学的解析

    第46回歯科基礎医学会学術大会ならびに総会  2004 

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  • ラット顎下腺に分布する感覚神経の経路に関する組織化学的研究

    第46回歯科基礎医学会学術大会ならびに総会  2004 

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  • 最高野ニューロンにおける過分極作動性カチオン電流(Ih)のプロポフォールに対する感受性

    第44回歯科基礎医学会学術大会ならびに総会  2004 

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  • ラット顎下腺からの求心性情報の電気生理学的解析

    第46回歯科基礎医学会学術大会ならびに総会  2004 

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  • 自律神経支配から見た唾液分泌機構ー電気生理学的解析

    第46回歯科基礎医学会学術大会若手サテライトシンポジウム 「唾液腺機能制御機構解析法の最前線線」  2004 

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  • ラット上唾液核細胞における興奮性の反復シナプス入力に対する発火特性

    第46回歯科基礎医学会学術大会ならびに総会  2004 

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  • 顎下腺・舌下腺および舌を支配するラット上唾液核ニューロンのシナプス応答

    第81回日本生理学会大会  2004 

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  • ラット最高野ニューロンのセロトニン(5-HT)感受性

    第76回日本薬理学年会・第80回日本生理学会大会  2003 

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  • ELECTROPHYSIOLOGICAL ANALYSIS OF THE AFFERENT NEURAL ACTIVITY FROM THE SUBMANDIBULAR SALIVARY GLAND IN RATS.

    Society for Neuroscience 33rd Annual Meeting 2003  2003 

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  • Facilitation of glutamate release by the activation of presynaptic 5-HT3 receptors in rat area postrema neurons.

    Society for Neurosience 33rd Annual Meeting  2003 

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  • ラット上唾液核の抑制生シナプス後電流はシナプス後膜のGABAB受容体を介して調節される。

    第76回日本薬理学年会・第80回日本生理学会大会  2003 

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  • ラット上唾液核細胞における抑制性シナプス伝達はGABAB受容体を介する

    第44回歯科基礎医学会学術大会ならびに総会  2002 

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  • 唾液腺を支配するラット上唾液核細胞の抑制性入力の解析

    第79回日本生理学会大会  2002 

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  • ラット最高野ニューロンにおけるH電流の特性

    第79回日本生理学会大会  2002 

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  • Suppression of the hyperpolarization-activated inward current contributes to the inhibitory actions of propofol on the epileptiform activities of hippocampal neurons.

    第32回北米神経科学  2002 

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  • 最高野におけるセロトニン(5-HT)受容体による神経活動の調節メカニズム

    第23回岡山歯学会総会  2002 

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  • 過分極作動性内向き電流(Ih)によるラット最後野神経活動の制御機構

    第44回歯科基礎医学会学術大会ならびに総会  2002 

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  • Excitability of area postrema neurons controlled by the hyperpolarization-activated inward currents.

    第32回北米神経科学  2002 

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  • PropofolのH電流抑制作用に関する電気生理学的検討

    第79回日本生理学会大会  2002 

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  • スライスパッチクランプ法によるラット最高野ニューロンの膜特性解析

    第43回歯科基礎医学会総会  2001 

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  • 海馬CA1ニューロンのH電流に対するプロポフォールの抑制作用

    第43回歯科基礎医学会総会  2001 

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  • ラット上唾液核細胞の興奮性および抑制性入力の解析

    第15回唾液腺談話会  2001 

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  • Enhancement of synaptic transmission induced by burst responses of the deep layer neurons in the entrohinal cortex and the parasubiculum.

    第23回神経科学大会・第10回神経回路学会大会合同大会  2000 

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  • Excitatory and inhibitory postsynaptic currents recorded from the superior salivatory neurons in rats.

    International Society for Autonomic Neuroscience (ISAN)  2000 

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  • Electrophysiological analysis of sharp-wave associated gamma-frequency ocillation in the retorohippocampal cortices and amygdala in rat brain slice.

    International Society for Autonomic Neuroscience (ISAN)  2000 

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  • てんかん様バースト発火に対するプロポフォールの抑制機序の検討

    第42回歯科基礎医学会総会  2000 

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  • ラット脳スライスを用いた海馬CA1ニューロンのバースト発火に対するプロポフォールの抑制機序の検討

    第21回岡山歯学会総会  2000 

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  • 舌、顎下腺・舌下腺を支配するラット上唾液核細胞のシナプス入力の解析

    第42回歯科基礎医学会総会  2000 

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  • 海馬体および扁桃体ニューロンの膜特性および神経連絡網

    海馬体および扁桃体ニューロンの膜特性および神経連絡網  2000 

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  • Role of the parabrachial nucleus in salivation induced by unpalatable taste in rats.

    International Society for Autonomic Neuroscience (ISAN)  2000 

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  • 舌、顎下腺及び舌下腺を支配する上唾液核細胞の形態学的解析

    第76回日本生理学会大会  1999 

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  • カエル舌咽神経の塩応答に対するアミロライドの効果

    第31回東北生理談話会  1999 

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  • 海馬体および扁桃体ニューロンの膜特性および神経連絡網

    第41回歯科基礎医学会学術大会ならびに総会  1999 

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  • 舌、顎下腺・舌下腺を支配するラット上唾液核細胞の形態学的特徴と膜特性

    第20回岡山歯学会総会  1999 

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  • 扁桃体単一ニューロン特性および海馬体との神経連絡に関する電気生理学的検討

    第76回日本生理学会大会  1999 

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  • 舌と顎下腺・舌下腺を支配するラット上唾液核細胞の形態学的特徴

    第41回歯科基礎医学会学術大会ならびに総会  1999 

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  • Effects of appetite-boosting peptides on the superior salivatory nucleus neurons in rats

    Yoshihiro Mitoh, Tadasu Sato, Takehiro Yajima, Masako Fujita, Hiroyuki Ichikawa, Motoi Kobashi, Ryusuke Yoshida

    The 97th Annual Meeting of the Physiological Society of Japan 

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    Language:English   Presentation type:Poster presentation  

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Research Projects

  • 口腔機能低下症に迷走神経刺激は有効か:脳腸連関によるニューロモジュレーション解析

    Grant number:22K10246  2022.04 - 2025.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    植田 紘貴, 吉田 竜介, 美藤 純弘

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

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  • 新技術を用いた革新的包括的自律神経研究の拠点形成

    2021.10 - 2022.03

    岡山大学  「令和3年度岡山大学次世代研究育成グループ」事業 

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    Grant amount:\500000

  • The raison d'etre of classical synapses in taste buds

    Grant number:21H03106  2021.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    吉田 竜介, 美藤 純弘, 樽野 陽幸, 池亀 美華

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    Grant amount:\17420000 ( Direct expense: \13400000 、 Indirect expense:\4020000 )

    本年度は、本研究で用いる以下の遺伝子改変マウスを作成した。(1)味蕾においてGABA合成酵素であるGAD67を欠損するマウス(K5-Cre;GAD67-flox)、(2)味蕾においてGABA合成酵素であるGAD67を欠損しGFPを発現するマウス(K5-Cre;GAD67-GFP/flox)、(3)味蕾においてシナプス関連遺伝子SNAP25を欠損するマウス(K5-Cre;SNAP25-flox)、(4)味蕾内でIII型細胞のみで発現する遺伝子を欠損するマウス2種(TypeIII-A-KO、TypeIII-B-KO)。今後、(3)または(4)かつGAD67-GFPを発現するマウス、(1)~(4)かつTRPV1を欠損するマウスを順次作成する予定である。また、K5-Creの味蕾での発現を確認するため、GAD67-GFPを発現し、K5発現細胞でtomatoの発現を誘導するマウス(K5-Cre;ROSA26-tomato;GAD67-GFP)を作成し、GAD67発現細胞(III型細胞)を含む味蕾細胞でK5-Creが発現することを確認した。さらに免疫組織化学的実験により、(2)のマウスにおいて味蕾内GFP発現細胞でGAD67発現が消失し、他の味細胞マーカー遺伝子の発現は変化しないことを確認した。
    次に、これらマウスを作成するために用いた各種遺伝子改変マウス(K5-Cre、GAD67-flox、SNAP25-flox、TRPV1-KO)の味覚行動応答について短時間リック法にて調べた。その結果、これらのマウスは各種味溶液(ショ糖、キニーネ、NaCl、グルタミン酸ナトリウム、HCl、クエン酸など)に対し野生型マウスとほぼ同様の応答を示すことを確認した。ただし、TRPV1-KOマウスに関してはカプサイシンに対する忌避反応が減弱していた。

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  • おいしく食べるための唾液、その中枢神経機構の解明

    Grant number:21K11697  2021.04 - 2024.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    美藤 純弘, 向井 康敬

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    マウスは遺伝子組換えの種類が豊富なので、本研究課題はマウスを使った測定系を確立し分析を進める予定であった。しかし、共同研究者の向井らがオレキシンCreラットを開発したので、これまでのラットにおける研究成果を生かすためにもラットで行うことにした。本研究ではラット視床下部外側野ニューロンを電気刺激あるいは光刺激したときの上唾液核ニューロンの応答や唾液分泌を調べる予定であるが、そのためには視床下部外側野に電気刺激または光刺激するための光ファイバーを刺入する位置を特定する必要がある。そこで上唾液核ニューロンに投射する視床下部外側野ニューロンの分布を検討するために、上唾液核に蛍光色素を投与し、逆行性軸索輸送により視床下部外側野ニューロンを染色した。上唾液核(吻尾側方向に500マイクロメートル、背腹方向に500マイクロメートル)に局所的に色素注入するのは精密な技術を要するためにまだ成功例が少ないが(n=2)、標識ニューロンは視床下部外側野において吻尾側方向に広範囲に渡って分布しているように思われた。この標識ニューロンのうちオレキシン産生ニューロンはどれくらい割合で存在し、またどのように分布しているか、オレキシンに対する免疫染色を行うことにより検討中である。この実験は本研究において重要な部分で、刺激部位について確証を得るために現在集中的に行なっている。一方、オレキシンニューロンを特異的に興奮させるために、470 nm光で細胞を活性化させるチャネルロドプシン2をオレキシンニューロンに組み込むことを試みている。

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  • A study on brain mechanisms in which mental activity influences salivary secretion

    Grant number:18K11022  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Mitoh Yoshihiro

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    The effects of dopamine (DA), serotonin (5HT), and noradrenaline (NA) on the rat superior salivary nucleus neurons, which is the parasympathetic center of the submandibular and sublingual salivary glands, were investigated using slice patch clamp method. DA and 5HT generated inward currents, but not NA. DA also generated outward currents. 5HT and NA increased the frequency of miniature excitatory postsynaptic currents, but not DA. Immunohistochemical studies for DA receptors demonstrated that the neurons had immunoreactivities for D1-like receptors involved in excitatory effects, and those for D2-like receptors involved in inhibitory effects. These results suggest that salivary secretion may change with mental condition.

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  • 精神活動により影響される唾液分泌に関する研究

    Grant number:17K00921  2017.04 - 2020.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    藤田 雅子, 美藤 純弘, 松尾 龍二, 小橋 基

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

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  • Study for regulatory mechanism of feeding-related phenomena by GLP-1

    Grant number:15K00818  2015.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kobashi Motoi

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

    The effects of glucagon like peptide-1 (GLP-1), which is appetite-reducing peptide, on reflex swallowing were examined using anaesthetized rats. GLP-1 suppressed reflex swallowing via the medial part of the NTS in the dorsal medulla. Orexin-A, which is appetite enhancing peptide, also suppressed reflex swallowing. The administration of orexin-A prior to the injection of GLP-1 attenuated the degree of suppression of the swallowing response induced by GLP-1-administration. Suppression of reflex swallowing by appetite-related peptides is thought to be helpful in keeping the ability of reflex swallowing constant in cooperation with the suppression ofappetite-enhancing peptides.

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  • Neural mechanisms of salivary secretion related to oral senses and mastication.

    Grant number:26462811  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MATSUO Ryuji, Carpenter Guy H.

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

    The neural mechanism for salivary secretion induced by mastication and oral senses was investigated by electrophysiological techniques in the rat. As the result, we found that oral senses are cue sign for starting and determining patterns of both mastication and salivation. This suggests that salivation is not a result of mastication or oral sensory information. Secreted saliva dissolves foods and helps to make sense of taste, affecting taste quality and intensity. Moreover, saliva protects taste receptors in the oral cavity. Mastication, salivation, and oral senses are affected each other.

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  • A study on mechanisms regulating salivary secretion during feeding

    Grant number:26500009  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    FUJITA Masako

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    It is most likely that salivary secretion during feeding is regulated by the lateral hypothalamic area (LH). We investigated the effects of melanin concentrating hormone (MCH) which is a feeding promoting peptide localized in the LH, on superior salivatory nucleus (SSN) neurons, which is the primary center of the parasympathetic nervous systems for the submandibular and sublingual glands. No SSN neurons exhibited immunoreactivity for MCH receptor and responded to MCH application. However, in the same recording neurons, orexin, a feeding promoting peptide localized in the LH as with MCH, showed excitatory responses. Therefore, regulation of SSN neuronal activity by LH would be conducted by other transmitters including orexin.

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  • Approach to Educate HACCP in Schools of Medicine, Dentistry and Pharmacy

    Grant number:26670261  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Kato Masahiko, KONNO Katsuhiko

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    Grant amount:\2860000 ( Direct expense: \2200000 、 Indirect expense:\660000 )

    A questionnaire on hazard analysis and critical control points (HACCP) was conducted among students in schools of dentistry and pharmacy in 2014. The results suggested that students did not have adequate understanding of HACCP. We gave training on HACCP application to pharmacy students in 2015 using commercially available textbooks. After the training, we collected student-written documents and distributed another questionnaire on HACCP. The next year (2016), we then performed the training and evaluation a second time using textbooks that we created ourselves. The number of errors in the student-written documents was higher and the average score on the questionnaire was lower in 2015 than in 2016, suggesting that our textbook is effective. We have revised our textbook accordingly, which we are publishing as “HACCP for Students”.

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  • A study for role of the feeding center in submandibular and sublingual salivary secretion

    Grant number:25462887  2013.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Mitoh Yoshihiro, MATSUO RYUJI, KOBASHI MOTOI, FUJITA MASAKO

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    Grant amount:\4940000 ( Direct expense: \3800000 、 Indirect expense:\1140000 )

    Using free-moving rats, we examined the salivation when rats were provided with diets with various water contents. In sham-operated rats, salivation was decreased with increase of water contents in diets (powder > hard pellet > hard mash > medium mash > soft mash). Lesions of feeding center largely reduced the salivation although the tendency for salivary volume was maintained. In the superior salivatory nucleus (SSN) neurons which is the primary parasympathetic center of the submandibular and sublingual salivary glands in rats, effects of orexins and melanin-concentrating hormone (MCH), which were a feeding stimulator that were specifically produced in the lateral hypothalamic area (feeding center). SSN neurons were excited by orexins via orexin receptor 1 and 2 with decrease of potassium conductance, but not MCH. Excitation of SSN neurons via orexin may be involved in abundant salivation in feeding.

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  • Analysis of neural network for maintenance salivary secretion

    Grant number:23592731  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MATSUO RYUJI, KOBASHI Motoi, TERAYAMA Ryuji, MITOH Yoshihiro, FUJITA Masako

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    Grant amount:\5070000 ( Direct expense: \3900000 、 Indirect expense:\1170000 )

    The neural circuit for regulation of salivary secretion was investigated by anatomical and electrophysiological techniques. Our histochemical study shows that the superior salivatory nucleus in the lower brainstem (parasympathetic neurons innervating the submandibular and sublingual salivary glands) has heavy connection with the lateral hypothalamic area (feeding center). Our electrophysiological study also shows that main neural circuit for vigorous salivation is composed of the cerebral cortex of masticatory area, lateral hypothalamic area, and superior salivatory nucleus. It is suggested that the texture of food is recognized in the cerebral cortex that forms the command for salivation and mastication suitable for the recognized food. This salivary function may be maintained by visceral afferents form the salivary glands.

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  • Central orexin-A inhibits reflex swallowing via caudal brainstem

    Grant number:22592064  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBASHI Motoi, SHIMATANI Yuichi, MITOH Yoshihiro, MATSUO Ryuji, FUJITA Masako

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    We examined the effects of orexins on the reflex swallowing using anaesthetized rats. Orexins were administered into the fourth ventricle. Swallowing was induced by repeated electrical stimulation of the central cut end of the superior laryngeal nerve (SLN) and was identified by the electromyogram lead penetrated the mylohyoide muscle through bipolar electrodes. The frequency of swallowing during the electrical stimulation of the SLN decreased after the administration of orexin-A in a dose-dependent manner. The latency of the first swallowing tended to be extended after the administration of orexin-A. The administration of orexin-B did not affect swallowing frequency. Pre-administration of SB334867, an orexin1 receptor antagonist, attenuated the degree of inhibition of swallowing frequency induced by the administration of orexin-A. To identify the effective site of orexin-A, the effect of a microinjection of orexin-A into the dorsal vagal complex (DVC) was evaluated. Orexin-A was injected into one of the lateral DVC, the intermediate DVC, or the medial DVC. Microinjection of orexin-A into the medial DVC but not the other two sites decreased swallowing frequency. Pre-injection of SB334867 into the medial DVC disrupted the inhibitory response induced by fourth ventricular administration of orexin-A. The electrical lesion of the commissural part of the NTS, but not ablation of the AP, abolished the inhibition of reflex swallowing induced by fourth ventricular administration of orexin-A. These results suggest that orexin-A inhibits reflex swallowing via orexin1 receptors situated in the commissural part of the NTS and/or its vicinity.

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  • Reguraltory mechanisms of neuronal activity in the superior salivatory nucleus by feeding-related peptides.

    Grant number:21592361  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MITOH Yoshihiro, MATSUO Ryuji, KOBASHI Motoi, FUJITA Masako, ICHIKAWA Hiroyuki

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    The superior salivatory nucleus(SSN) neurons which is the primary parasympathetic center of the submandibular and sublingual salivary glands in rats were excited by orexins, one of feeding-related peptides, from lateral hypothalamic neurons(feeding center). The excitation in SSN neurons was completely inhibited by antagonists for OX1R and OX2R, orexins receptors subtypes. Additionally, SSN neurons showed immunoreactivities for OX1R and OX2R, suggesting that the excitation is mediated by OX1R and OX2R. Orexin-induced excitation in SSN neurons may be involved in abundant salivation in feeding.

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  • Study on the glutamatergic inputs from the forebrain and brainstem to the neurons innervating submandibular salivary glands

    Grant number:19592143  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MITOU Yoshihiro, MATUO Ryuji, KOBASHI Motoi

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

    麻酔下ラット唾液分泌神経(上唾液核)にグルタミン酸バイオセンサーを挿入し、味覚や機械刺激に対する応答を分析した。正常および切断除脳を行ったラットのパッチクランプ実験で、上唾液核は口腔感覚情報を中継している下位脳幹からのグルタミン酸入力の他に、前脳からもグルタミン酸入力を受けていることが示唆された。自由行動下のラットで摂食中、摂食中枢にグルタミン酸入力をブロックする薬物を投与すると唾液分泌は減少した。よって、摂食中の唾液分泌には、下位脳幹からの興奮性入力以外に摂食中枢など前脳からの興奮性入力が重要であることが示唆された。

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  • Central ghrelin inhibits reflex swallowing and induces gastric relaxation of the rats

    Grant number:19592144  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBASHI Motoi, MATSUO Ryuji, MITOH Yoshihiro, TSUKAMOTO Goichi

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

    空腹を起こし、その結果食事の量を増やす作用を持つグレリンという物質の作用を、麻酔を施したラットを用いて検討した。グレリンを脳に投与すると胃の弛緩が生じ、嚥下の頻度が減少することが明らかとなった。胃の弛緩は食事の量が増えても胃に適切に食事が収まるように、胃の容量を広げてやる作用があることを示している。嚥下の頻度の減少の意味を明らかにするには、さらなる研究が必要である。

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  • 唾液核に対する興奮性入力の解析-グルタミン酸バイオセンサーによる行動学的測定法一

    Grant number:18659552  2006 - 2007

    日本学術振興会  科学研究費助成事業  萌芽研究

    松尾 龍二, 小橋 基, 美藤 純弘

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    Grant amount:\3300000 ( Direct expense: \3300000 )

    唾液分泌の神経制御は、脳幹部における反射と上位中枢からの下行性制御に区分して論じられている。本研究では、特に摂食行動に関係の深い上位中枢(視床下部外側野、大脳皮質味覚野と咀嚼野)からの興奮性入力(グルタミン酸作働性)を動物実験により検討する。具体的には唾液分泌の副交感神経中枢である上唾液核細胞に対する上位中枢からの興奮性入力量とそれに伴う唾液分泌動態を分析する。とくに本実験計画では、興奮性入力量をグルタミン酸バイオセンサーを用いて解析する。本年度は、1.グルタミン酸バイオセンサーを急性実験と慢性実験に適用した。2.免疫組織学的に上位中枢の興奮性細胞と抑制性細胞を染色した。3.脳スライス標本で唾液核への入力を電気生理学的に検索した。
    1.麻酔下動物(Wistar系雄性ラット)にて、口腔領域の味覚刺激によって唾液分泌を誘発した。同時に上唾液核のグルタミン酸変動をグルタミン酸バイオセンサーで観察し、定量的に解析した。その結果、グルタミン酸バイオセンサーの変動は味覚刺激では小さかった。慢性実験では、とくに摂食行動中に変動が大きく、摂食に関連する中枢(視床下部外側野、扁桃体)の影響が大きいことが示唆された。
    2.免疫組織学的実験により、上唾液核に入力する神経を検索した。その結果、上位中枢(視床下部外側野、扁桃体、大脳皮質味覚野と咀嚼野)には興奮性細胞(グルタミン酸作働性)が多数存在し、抑制性細胞は極めて少数であることが分かった。
    3.電気生理学的に、上唾液核細胞は興奮性と抑制性の入力を受けるが、両者はともに大きな膜電流の変化を発生させた。これは基本的に脳幹部に抑制性神経が多く存在することを示唆するものであった。
    以上の結果より、上唾液核細胞は、摂食行動中に主に上位中枢からは興奮性入力を受け、抑制性入力は脳幹部の介在神経から受けることが示唆された。

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  • Analysis of the functional and biological roles of the hyperpolarization-activated cation current in the central nervous system,

    Grant number:17591937  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    FUNAHASHI Makoto, SOGAWA Chiharu, MITOH Yoshihiro, SOGAWA Norio, MATSUO Ryuji

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    Grant amount:\3500000 ( Direct expense: \3500000 )

    We performed whole-cell patch-clamp recordings from area postrema neurons to investigate the functional and biological roles of the hyperpolarization-activated cation current (Ih).
    1) Morphological properties
    Using electrophysiological criteria, AP neurons were subdivided into three groups : 1) cells displaying both the hyperpolarization-activated cation current (I_h) and the fast transient outward current (fast I_<to>) ; 2) cells displaying only the fast I_<to> ; and 3) cells displaying only the slow Ito. All AP neurons had a single axon that was distinctly thinner than the cells' dendrites. No systematic differences, across groups, in the orientation of dendrites or axons were identified. Mean values of cell size and capacitance of neurons from group 3 were significantly larger than those of the other groups. Interestingly, a number of cells from group 1 and 3 but not group 2 were found to extend their dendrites into the nucleus tractus solitarius (NTS), suggesting that AP neurons could receive vagal afferent inputs at their dendritic termini within the NTS. Although the AP have been implicated to contain uniformly shaped neurons, this study indicates the presence of significantly different subpopulations of AP neurons, which were characterized not only electrophysiologically but also morphologically.
    2) Sensitivity to ATP
    Most area postrema neurons responded to ATP application, and most responses were excitatory. Voltage-clamp recordings showed three different types of response : 1) a postsynaptic or extrasynaptic excitatory response (inward currents ; n=26/51 cells), 2) a presynaptic excitatory response (increased frequency of miniature excitatory postsynaptic currents with only a small direct postsynaptic current; n=24/51 cells, or 3) a postsynaptic inhibitory response (outward current ; n=1/51). The excitatory responses were found in both of the two major electrophysiological cell classes, i.e. cells displaying I_h and cells not displaying I_h, while the inhibitory responses were found in only cells not displaying I_h. Current-clamp recordings showed ATP-induced depolarization (n=13/15) or hyperpolarization (n=2/15) of membrane potential that modulated the frequency of action potentials. In the presence of CNQX, mEPSCs were abolished and bath applied ATP did not generate mEPSCs, indicating that glutamate release was facilitated by the activation of presynaptically located ATP receptors. Our pharmacological results from studies with ATP, aβme-ATP, βyme-ATP and PPADS indicate that P2X_2, P2X_5 and P2X_7 are the most likely subunits which compose the P2X receptor in the post-and/or extrasynaptic regions. We conclude that half of the presynaptic P2X receptors are most likely composed of P2X_2, P2X_5 and P2X_7 subunits while the others also contain P2X_1 subunits. It is well known that P2X_7 subunit forms only homomultimeric P2X receptors. Finally, the present study suggests that purinoceptor activation may contribute to the control of several autonomic functions by area postrema neurons.

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  • Electrophysiological study on development of inhibitory synaptic transmission in central neurons involved in oral function.

    Grant number:17591935  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MITOH Yoshihiro, MATSUO Ryuji, FUNHASHI Makoto

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    Grant amount:\2800000 ( Direct expense: \2800000 )

    We showed the excitatory (glutamate) and inhibitory (GABA and glycine) synaptic inputs to superior salivatory (SS) neurons in neonatal rat brainstem slices. There is a possibility that the synaptic transmission to SS neurons develop postnatally with the development of oral function. In the present study, we studied the development of the inhibitory synaptic transmission to SS neurons electrophysiologically. We used Wistar rats at postnatal day 2 (P2) to P14. The SS neurons innervating the submandibular salivary glands and tongue were labeled by retrograde axonal transport of a fluorescent dye. Gramicidin perforated patch-clamp recordings from the labeled cell were performed. To examine the reversal potential (V_<rev>), the inhibitory postsynaptic currents (IPSCs) were evoked by electrical stimulation near the recording cell at various potentials. Additionally, to examine the effect of GABA_A receptor activation on the excitability of the cells, GABA (1 mM, 100 ms) was applied via pressure ejection near the recording cell at its resting potential. The V_<rev> was shifted with age, and that at P2-P4, P5-P7 and P8-P14 were-52.6 ± 5.1 mV (n = 9),-62.3 ± 1.6 mV (n = 12) and-71.4 ± 1.5 mV (n = 12), respectively. Exogenous GABA application produced depolarization in 40 % cells at P2-P4, and produced hyperpolarization after P8. Such functional change of synaptic transmission might be involved in the transition from sucking to mastication.

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  • The study for functional correlation between palatability and gastric motility induced by appetite-enhancing peptides.

    Grant number:17591936  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBASHI Motoi, TSUKAMOTO Goichi, MATSUO Ryuji, MITOH Yoshihiro

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    Grant amount:\3400000 ( Direct expense: \3400000 )

    The functional correlation between palatability and gastric motility induced by appetite-enhancing peptides were investigated in this study. The effects of neuropeptide Y (NPY) on motility of the proximal stomach were examined in anaesthetized rats. The administration of NPY into the 4th ventricle induced relaxation of the proximal stomach in a dose-dependent manner. The administrations of Y1 receptor (Y1R) agonist induced relaxation potently rather than those of NPY. The microinjections of Y1R agonist into the caudal part of the dorsal vagal complex (c-DVC) induced relaxation of the proximal stomach. The administration of NPY into the 4th ventricle did not induce relaxation after bilateral injection of Y1R antagonist into the c-DVC. These results revealed that NPY induced the relaxation in the proximal stomach via Y1R situated in the DVC. The effect of ghrelin on motility of the proximal stomach was also examined. The administration of ghrelin into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Simultaneous administration of ghrelin and GHS-R antagonist did not induce significant change in IGP. Microinjections of ghrelin into the c-DVC induced relaxation of the proximal stomach. These results indicate that ghrelin induces the relaxation of the proximal stomach via the GHS-R situated in the DVC as well as NPY. These results strongly suggest that the appetite-enhancing peptide facilitate reservoir function of the stomach to accommodate body to overconsumption elicited by the appetite-enhancing neuropeptides. However, the administration of the other appetite-enhancing peptides, melanin-concentrating hormone (MCH), did not induce gastric response. Intracerebroventricular (ICV) administrations of orexin, MCH and NPY increased the intake of saccharin. Drinking of saccharin in turn elevated the mRNA levels of orexin and NPY, but not MCH. Pre-treatments of naloxone, an opioid antagonist, blocked the orexigenic effects of orexin and NPY. These results suggest that the overconsumption promoted by sweet and palatable tastes is attributed to the activation of orexigenic neuropeptides, such as orexin and NPY, and a downstream opioid system together with enhanced digestive functions.

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  • Mechanisms Involving in the Inhibition of Nitric Oxide-Mediated Lower Esophageal Sphincter Relaxation Induced by Volatile Anesthetics in Rabbits.

    Grant number:15592110  2003 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MITOH Yoshihiro, MIYAWAKI Takuya, MATSUO Ryuji

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    Grant amount:\3500000 ( Direct expense: \3500000 )

    Nonadrenergic noncholinergic (NANC) nerves, which regulate peristaltic waves and/or relaxing mechanisms of the gastrointestinal tract, are known to be nitrergic and to initiate NO-cGMP signaling pathway. We investigated the effect of sevoflurane on NANC relaxation of the lower esophageal sphincter (LES), and the relevance of peripheral N-methyl-D-aspartate (NMDA) receptors in the myenteric plexus mediating NANC relaxation. Sevoflurane inhibited NANC relaxation in a concentration-dependent manner. MK801 concentration-dependently inhibited NANC relaxation, accompanied by a decrease in cGMP production. NMDA induced a concentration-dependent relaxation, which is antagonized by MK801. NMDA stimulated cGMP production, which was inhibited by N^G-nitro-L-arginine. Superoxide dismutase (SOD) shifted the concentration-response relationship of MK801 mediating inhibition of NANC relaxation to the right, but catalase did not. Treatment with diethyldithiocarbamic acid to inactivate Cu/Zn SOD shifted the concentration-response relationships of pyrogallol, ketamine, and MK801 mediating the inhibition of NANC relaxation to the left. These findings suggest that the peripheral NMDA receptors mediates NANC smooth muscle relaxation, and modulates it in part through extracellular production of superoxide anion thus eliminating the relaxant effect of endogenous NO, and that volatile anesthetics may modify LES function by modulating NANC relaxation through antagonism of peripheral NMDA receptors. The functional linkage of peripheral NMDA receptors in the myenteric plexus and NO-cGMP pathway leading to smooth muscle relaxation could provide a key on elucidating the roles of peripheral excitatory amino acids and endogenous NO regulating gastrointestinal motility in the near future.

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  • Analysis of the functional role of the hyperpolarization-activated cation cunert within the centaral nervous system.

    Grant number:15591965  2003 - 2004

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    FUNAHASHI Makoto, SOGAWA Chiharu, MITOH Yoshihiro, MATSUO Ryuji

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    Grant amount:\3500000 ( Direct expense: \3500000 )

    This study elucidated the membrane properties, morphology and chemosensitivities of area postrema neurons using a patch-clamp technique in rat brain slices. Results are summarized as below.
    1)The activation of the hyperpolarization-activated cation current (I_h) was identified in approximately 62% of area postrema neurons tested. Extracellular Cs^+ ions (2 mM) and ZD7288 (100 mM), a potent selective I_h channel antagonist, blocked I_h and induced a membrane potential hyperpolarization, suggesting the sustained activation of I_h near the resting potential and a contribution from I_h to membrane potential maintenance at more depolarized levels. ZD7288 decreased the spontaneous discharge rate by prolonging the slow depolarization between two spikes, with minimal effect on the amplitude of the afterhyperpolarization or action potential waveforms. I_h stabilized the latency of rebound action potentials. I_h was weakly activated by external 8-bromoadenosine 3,5, cyclic monophosphate (1 mM) or forskolin (50-100 mM), indicating that the I_h channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that I_h contributes to the subthreshold membrane and firing properties of rat area postrema neurons and may regulate their resting membrane potential and firing patterns.
    2)mEPSCs and evoked EPSCs were completely blocked in media containing the non-NMDA ionotropic receptor antagonist, CNQX (10 μM), indicating that EPSC were glutamate events.
    3)Excitatory responses to the bath application of nicotine (50 μM) were found in approximately 78% (35/45) of all cells tested. Responsive cells included both the cells that display the hyperpolarization-activated cation current (Ih) and cells that do not display Ih. An inhibitory effect of nicotine was never seen. We conclude that nicotinic receptors in the rat area postrema can excite cells via (1)a direct post- and/or extrasynaptic mechanism ; and (2)an indirect enhancement of glutamate release.
    4)The bath application of serotonin (5-HT, 50 μM) or phenylbiguanide (PBA, 50 μM, a potent 5-HT_3 receptor agonist) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) or miniature EPSCs (mEPSCs) in 35 of 83 neurons (42%). These increases occurred in all electrophysiological cell classes. No cells exhibited a decrease in EPSC frequency. These results suggest that glutamate release is increased in the area postrema by presynaptic 5-HT_3 receptor activation. Further, we present evidence that 5-HT_3 receptor activation may be able to directly release glutamate from terminals, by-passing a requirement for voltage-dependent calcium entry into terminals. Such a mechanism may contribute to the chemosensitive function of area postrema neurons.
    5)Although propofol suppressed Ih of area postrema neurons in a dose-dependent manner that was similar to what we observed for the hippocampal CA1 neurons, the IC_<50>, for I_h in area postrema neurons (38 mM) was more than six times less than that found for hippocampal CA1 neurons (235 mM). We conclude that rat area postrema neurons are exquisitely sensitive to propofol. Given that reductions of Ih are associated with decreased excitability in neurons, we believe that the known antiemetic effects of propofol anesthesia are at least partly a result of a direct action on area postrema neurons to lower their excitability.

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  • Electrophysiological analysis of impulse formation in the salivary secretory neurons

    Grant number:14370594  2002 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUO Ryuji, MITOH Yoshihiro, FUNAHASHI Makoto, KOBASHI Motoi

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    Grant amount:\9600000 ( Direct expense: \9600000 )

    The superior salivatory (SS) nucleus contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands and those innervating the anterior part of the tongue. To evaluate mechanisms of impulse formation, we analyzed postsynaptic currents of the SS neurons. The SS neurons were labeled by injection of fluorescent tracers into the peripheral course of the neurons in neonatal Wistar rats. Two days after the injection, the brainstem was sliced and whole-cell patch-clamp recordings were obtained from the labeled neurons. The whole-cell postsynaptic currents were evoked by electrical stimulation applied near the recording cell. The following results were obtained. 1) The SS neurons innervating the different targets scattered and intermingled in the lateral reticular formation of the medulla oblongata, which have 3-4 main dendrites that extended dorso-ventrally about 700 um. 2) The whole-cell currents were antagonized by bicuculline, strychnine, CPP, and CNQX, suggesting that major components of the postsynaptic currents are mediated by GABA_<A->, glycine-, NMDA-, and non-NMDA-receptors. 3) In the SS neurons for the salivary glands, the ratio of the NMDA component to the total excitatory postsynaptic currents was larger than that of the non-NMDA component, and the GABA_A component was larger than the glycine component. 4) Bath application of baclofen, GABA_B-receptor-agonist, reversibly and dose-dependently reduced the amplitude of the inhibitory postsynaptic currents in some neurons. No changes in the input resistance of the postsynaptic membrane were observed during application of baclofen. When paired electrical stimulation (50 ms interval) was applied, the amplitude ratio of the first and second postsynaptic currents was enhanced by baclofen. These results suggest existence of presynaptic GABA_B receptors. These characteristics of the synaptic inputs may be involved in determining the firing properties of the SS neurons.

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  • Electrophysiological analysis of brainstem neurons subserving autonomic and motor oral functions

    Grant number:11470391  1999 - 2000

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B).

    MATSUO Ryuji, MITOH Yoshihiro, FUNAHASHI Makoto, KOBASHI Motoi

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    Grant amount:\14100000 ( Direct expense: \14100000 )

    Neural network in the brainstem subserving autonomic and motor oral functions was investigated by electrophysiological and behavioral studies. In the electrophysiological study, biophysical properties of the superior salivatory (SS) neurons were analyzed by the whole-cell patch clamp technique in sliced brainstem preparations. Neural activity of the trigeminal motor neurons were also analyzed by the intra-cellular recording technique in sliced preparations. The SS neurons innervating the tongue displayed a prominent transient outward current (A-current), and fired up to 70 Hz. Those innervating the salivary glands expressed A-current lasting longer period, and fired up to 30 Hz. The SS neurons innervating the different targets scattered and intermingled in the lateral reticular formation of the medulla oblongata, which have 3-4 main dendrites that extended dorso-ventrally about 700 μm. The two kinds of SS neurons showed similar whole cell currents which of some neurons were antagonized by picrotoxin, 2-amino-5-phosphono-valeric acid (AP-5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that major components of the postsynaptic currents could be mediated by GABA_A-. NMDA- and non-NMDA-receptors. In behavioral study, salivary flow from the submandibular gland and activity of the masseter muscle were chronically recorded from the freely moving rats. During chewing. the amount of saliva and muscle activity were always parallel. When emesis was yielded by intravenous injection so apomorphine, salivary flow rate was correlated with movement of the stomach, but now with jaw movements.
    Through these studies, we conclude that the central nervous system integrates the autonomic and motor oral functions, and it is likely that a contact point between the two functions is situated in the lower brainstem especially the lateral reticular formation. The activity of the pre-motor neurons of the trigeminal motor nucleus should be analyzed in a new research project.

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  • Electrophysiological analysis of the lateral reticular formation controlling orofacial autonomic and motor functions

    Grant number:09470402  1997 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUO Ryuji, MASUDA Yuji, INOUE Tomio, MITHO Yoshihiro, FUNAHASHI Makoto

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    Grant amount:\13200000 ( Direct expense: \13200000 )

    Neural network in the brainstem subserving autonomic and motor oral functions was investigated by anatomical, electrophysiological and behavioral studies. In the anatomical study, FTTC and Rhodamine were injected into the anterior part of the tongue or the secretory nerve of the subamndibular gland, respectively, and the superior salivatory (SS) neurons innervating the tongue and those innervating the submandibular salivary glands were identified in rats. The two groups of SS neurons were similar in shape and intermingled in the lateral reticular formation. In the electrophysiological study, biophysical properties of the SS neurons were analyzed by the whole-cell patch clamp technique in sliced brainstem preparations. The SS neurons innervating the tongue displayed a prominent transient outward current (A-current), and fired up to 70 Hz. Those innervating the salivary glands expressed A current lasting longer period, and fired up to 30 Hz. Post-natal development of the A-currents was observed when we compared between A- currents of one-week and two-week old rats. In behavioral study, salivary flow from the submandibular gland and activity of the masseter muscle were chronically recorded from the freely moving rats, During chewing, the amount of saliva and muscle activity were not always parallel, suggesting different centrifugal effects on autonomic and motor functions.
    Through these studies, we conclude that the autonomic and motor oral functions are under control from the higher central nervous system, but there is a contact point between the two functions in the lower brainstem especially the lateral reticular formation. A further study is needed to clarify relationship between feeding behavior and blood flow rate of the tongue.

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  • 咽頭部および喉頭部の化学受容:Clイオンチャネルの関与

    Grant number:08771607  1996

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    美藤 純弘

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    Grant amount:\1000000 ( Direct expense: \1000000 )

    咽頭部、喉頭部を蒸留水(DW)やNa_2SO_4溶液で刺激すると嚥下が誘発される。NaCl溶液では嚥下が誘発されない。化学刺激による嚥下の誘発に、次のようなメカニズムが考えられた。粘膜の受容細胞にはClイオンチャネルがあり、水刺激では受容細胞の外側のClが少なくなり受容細胞が興奮し、NaCl刺激は受容細胞を抑制する。また、SO_4にはClイオンのチャネル透過性を増加させる作用があり、強い興奮作用を持つ。このように、化学刺激による嚥下にはClイオンチャネルの関与が考えられているが直接の証拠は得られていない。今回、喉頭蓋を支配する上喉頭神経神経から化学刺激による応答を記録し、これらの応答に対する種々Clイオンチャネル阻害剤の効果を調べた。
    ウレタン麻酔下のウサギをガラミンで非動化し、人工呼吸器で呼吸を維持し、喉頭蓋を露出した。喉頭蓋に刺激液を与え、上喉頭神経から応答を記録した。刺激液としてDW、154mM Na_2SO_4、154mM NaCl、及びそれぞれにClイオンチャネル阻害剤(SITS、furosemide、DPC、9-A-C)を0.1mM含有した溶液を使用した。刺激後のリンス溶液は154mM NaCLを用いた。DW、154mM Na_2SO_4の刺激で大きな応答が得られた。しかし、Clイオンチャネル阻害剤でこれらの応答は抑制されなかった。また154mM NaClに対する放電頻度にも影響はなかった以上、今回の実験では種々のClイオンチャネル阻害剤を使用したにもかかわらずそれらの薬物による効果は見られず、化学刺激による嚥下にはClイオンチャネルが関与する直接的証拠は得られなかった。そこで、Clイオンチャネルは受容細胞の表面膜でなく受容細胞間のタイトジャンクションより深い粘膜下の細胞膜にあり、Clイオンはタイトジャンクションを透過できるがClイオンチャネル阻害剤は透過できないので効果がなかったことが考えられる。

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  • Electrophysiological and microdialytic analysis on responses of dopaminergic and noradrenergic neurons in the medulla ablongata (A2aea)

    Grant number:05454502  1993 - 1994

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for General Scientific Research (B)

    ADACHI Akira, MITOH Y, KOBAYASHI M, KOBASHI M

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    Grant amount:\5700000 ( Direct expense: \5700000 )

    Responses of neurons within the nucleus taractus solitarius NTS) to gastric distension were analyzed. Though no primary afferents decrease their discharge rates in response to gastric distension, some NTS neurons decreased their discharage rate resoponding to this stimulus. Convergenece to this neuron of glucose responsive visceral afferent indicates the participation of NTS on control of ingestion.
    Further analysis of the glucose responsive neurons within the area postrema (AP) was made on the brain tissue slice preparations so that confirmed the existence of enteroceptor neuron within this structure.
    It was unable to detect change in dopamine release from the A2 area responding to gastric distension or intraperitoneal injection of LiCl. Futher analysis will be required after technical improvement.
    Homeostatic control of body fluid mediated by the branistem was analyzed by observing effects of portal infusion of hypertonic saline on the neural activity of the dorsal motor nucleus of vagus (DMV)
    The glucose responsive neurons were also found within the DMV.They might play a role on a fail safe mechanism as well as glycemic homeostatic control mediated by the brainstem.

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Other research activities

  • 歯学部先端領域研究センター(ARCOCS)セミナーへの参加

    2015

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    毎月開催される本セミナーに参加し、最先端の研究を学と同時に共同研究の可能性を探った。

 

Class subject in charge

  • tutorial (2023academic year) 1st semester  - 火4,火5,火6,火7

  • Physiology of animal function (2023academic year) 1st semester  - 水1,水2,水3

  • Oral Physiology (2023academic year) Third semester  - 水1~3,木4

  • Exercise for oral functions (2023academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2023academic year) 1st-4th semester  - その他

  • Physiology of vegetative function (2023academic year) Second semester  - 水1,水2,水3

  • Tutorial (2022academic year) 1st semester  - 火4,火5,火6,火7

  • Exercise for oral functions (2022academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2022academic year) 1st-4th semester  - その他

  • Tutorial (2021academic year) 1st semester  - 火4,火5,火6,火7

  • Exercise for oral functions (2021academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2021academic year) 1st-4th semester

  • Tutorial (2020academic year) 1st semester  - 火4,火5,火6,火7

  • Exercise for oral functions (2020academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2020academic year) 1st-4th semester  - その他

  • Tutorial (2019academic year) 1st semester  - 火4,火5,火6,火7

  • Exercise for oral functions (2019academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2019academic year) 1st-4th semester  - その他

  • Tutorial (2018academic year) 1st semester  - 火4,火5,火6,火7

  • Exercise for oral functions (2018academic year) Third semester  - 木5,木6,木7

  • Introduction to Dental Science (2018academic year) 1st-4th semester  - その他

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Social Activities

  • だ液のはたらき

    Role(s):Lecturer

    大学コンソーシアム岡山  R4年度前期「吉備創生カレッジ」講座  山陽新聞本社ビル  2022.4.16

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    Audience: High school students, College students, Graduate students, General

    Type:Lecture

  • 玉ねぎの切ったときの涙と唾液の分泌の関係について

    Role(s):Advisor

    フジテレビ  林修のニッポンドリル  2020.5

  • たかが唾液、されど唾液〜唾液が出ることの意味〜

    Role(s):Lecturer

    熊本県立宇土高等学校  2018.10.12

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    Audience: High school students

    Type:Visiting lecture

    スーパーサイエンスハイスクールに指定されている同校1・2年生約50人を対象として、唾液の生理学的意義と、その分泌の中枢神経機構について講義を行った。