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

researchmap

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

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

DOI： 10.3390/foods12061150

researchmap

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

DOI： 10.1016/j.autneu.2020.102712

researchmap

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

researchmap

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

DOI： 10.1016/j.neulet.2020.135041

researchmap

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

DOI： 10.1016/j.autneu.2017.05.010

researchmap

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

Web of Science

researchmap

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

Web of Science

researchmap

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

Web of Science

researchmap

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

CiNii Article

CiNii Books

researchmap

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

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

Web of Science

researchmap

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

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

Web of Science

researchmap

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

DOI： 10.1016/j.brainres.2014.11.026.

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本味と匂学会  

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。

researchmap

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

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

CiNii Article

CiNii Books

researchmap

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

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本味と匂学会  

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。

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J04102&link_issn=&doc_id=20130130230020&doc_link_id=%2Fcw7jasts%2F2012%2F001903%2F029%2F0365-0368%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2012%2F001903%2F029%2F0365-0368%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

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

Web of Science

researchmap

Language：Japanese   Publisher：日本味と匂学会  

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。

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J04102&link_issn=&doc_id=20120213140035&doc_link_id=%2Fcw7jasts%2F2011%2F001803%2F046%2F0327-0330%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2011%2F001803%2F046%2F0327-0330%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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.

DOI： 10.1016/j.regpep.2009.12.014

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

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.

DOI： 10.1152/ajpregu.00878.2007

Web of Science

researchmap

Language：English   Publishing type：Research paper (international conference proceedings)  

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.

DOI： 10.2152/jmi.56.267

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (international conference proceedings)  

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.

DOI： 10.2152/jmi.56.270

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (international conference proceedings)  

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.

DOI： 10.2152/jmi.56.264

Scopus

PubMed

researchmap

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

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.

DOI： 10.1016/j.brainres.2007.11.020

Web of Science

researchmap

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

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.

DOI： 10.1016/j.brainres.2007.06.003

Scopus

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本味と匂学会  

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。

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J04102&link_issn=&doc_id=20071228200030&doc_link_id=%2Fcw7jasts%2F2007%2F001403%2F040%2F0365-0368%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2007%2F001403%2F040%2F0365-0368%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

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.

DOI： 10.1152/ajpregu.00423.2005

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

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.

DOI： 10.1016/j.neures.2005.10.005

Web of Science

researchmap

Language：English   Publisher：OXFORD UNIV PRESS  

Web of Science

researchmap

Language：Japanese   Publisher：日本味と匂学会  

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。

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J04102&link_issn=&doc_id=20061227090044&doc_link_id=%2Fcw7jasts%2F2006%2F001303%2F077%2F0509-0512%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2006%2F001303%2F077%2F0509-0512%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

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.

DOI： 10.1016/j.brainres.2005.08.012

Web of Science

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本味と匂学会  

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

researchmap

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J04102&link_issn=&doc_id=20051229400003&doc_link_id=%2Fcw7jasts%2F2005%2F001203%2F008%2F0239-0242%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw7jasts%2F2005%2F001203%2F008%2F0239-0242%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROUS SCIENCE, SA  

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.

DOI： 10.1358/mf.2004.26.8.863726

Web of Science

researchmap

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

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.

DOI： 10.1016/j.brainres.2004.05.028

Web of Science

researchmap

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

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.

DOI： 10.1016/j.brainres.2004.04.043

Web of Science

researchmap

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

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.

DOI： 10.1016/j.brainres.2003.11.053

Web of Science

researchmap

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

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.

DOI： 10.1113/jphysiol.2003.047191

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

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.

DOI： 10.1016/S0168-0102(03)00003-8

Web of Science

researchmap

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

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

Web of Science

researchmap

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

researchmap

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

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

Web of Science

researchmap

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

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.

DOI： 10.1016/S0006-8993(02)02651-3

Web of Science

researchmap

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

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.

Web of Science

researchmap

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.

Web of Science

researchmap

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

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.

DOI： 10.1016/S1566-0702(01)00234-X

Web of Science

researchmap

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

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.

DOI： 10.1016/S0031-9384(98)00009-2

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

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.

Web of Science

researchmap

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

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.

DOI： 10.1093/chemse/22.6.613

Web of Science

researchmap

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

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.

DOI： 10.1093/chemse/21.1.65

Web of Science

researchmap

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

Web of Science

researchmap

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

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

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

Web of Science

researchmap

Responsible for pages：82-88  

researchmap

Responsible for pages：1-8  

researchmap

Language：Japanese

researchmap

researchmap

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

researchmap

Responsible for pages：339-342   Language：English

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：ヒョーロン・パブリッシャーズ  

CiNii Article

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2016270407

J-GLOBAL

researchmap

Language：Japanese   Publisher：The Japanese Pharmacological Society  

DOI： 10.1254/fpj.141.306

CiNii Article

CiNii Books

researchmap

Other Link： https://jlc.jst.go.jp/DN/JALC/10019820285?from=CiNii

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Web of Science

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：日本平滑筋学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：岡山歯学会  

researchmap

Language：Japanese   Publisher：岡山歯学会  

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：岡山歯学会  

ラットの新鮮脳海馬スライスにGABA A受容体拮抗薬ピクロトキシンを投与しててんかん様の自然発火を惹起させ,これにプロポフォールを投与したところ,濃度依存的に自然発火の頻度,持続時間が減少した.又,Schaffer側枝の電気刺激で惹起したてんかん様バースト発火に対しても,プロポフォールは濃度依存的に持続時間を減少させた.更にピクロトキシン及びAMPA型グルタミン酸受容体拮抗薬CNQX存在下でSchaffer側枝の電気刺激により誘発した興奮性シナプス後電位に対し,プロポフォール投与で振幅,持続時間は減少した.ピクロトキシン及びNMDA型グルタミン酸受容体拮抗薬CPP存在下での誘発電位に対してもプロポフォール投与は電位の持続時間を減少させた.次に細胞内パルス通電により生ずる海馬CA1ニューロンの膜電位変化に対し,プロポフォールを投与したところ,これらの膜電位変化は著明に減少した.プロポフォールが過分極作動性内向き電流(H電流)を抑制し,膜電位の過分極,膜抵抗の増加を引き起こすことが示された

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：歯科基礎医学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：The Japanese Association for the Study of Taste and Smell  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：The Japanese Association for the Study of Taste and Smell  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：日本味と匂学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：日本味と匂学会  

CiNii Article

CiNii Books

researchmap

Language：Japanese   Publisher：日本味と匂学会  

CiNii Article

CiNii Books

researchmap

Event date： 2024.10.19 - 2024.10.20

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Event date： 2024.9.11 - 2024.9.13

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2024.3.28 - 2024.3.30

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.11.25 - 2023.11.26

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.11.25 - 2023.11.26

Language：English   Presentation type：Oral presentation (general)  

researchmap

Event date： 2023.11.25 - 2023.11.26

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.16 - 2023.9.18

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.16 - 2023.9.18

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.11 - 2023.9.13

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.11 - 2023.9.13

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.11 - 2023.9.13

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.9.11 - 2023.9.13

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.8.1 - 2023.8.4

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.3.14 - 2023.3.16

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2023.3.14 - 2023.3.16

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2022.12.11

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Event date： 2022.10.29 - 2022.10.30

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Event date： 2022.8.22 - 2022.8.24

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2022.8.22 - 2022.8.24

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2021.3.28 - 2021.3.30

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2020.9.11 - 2020.10.9

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2020.5.15 - 2020.5.17

Language：Japanese   Presentation type：Poster presentation  

researchmap

Event date： 2020.3.17 - 2020.3.19

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2019.12.15

Language：Japanese   Presentation type：Oral presentation (general)  

researchmap

Event date： 2019.10.12 - 2019.10.14

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2019.9.17 - 2019.9.19

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2019.3.28 - 2019.3.30

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2019.3.28 - 2019.3.30

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2018.9.5 - 2018.9.7

Language：English   Presentation type：Poster presentation  

researchmap

Event date： 2018.3.28 - 2018.3.30

Language：Japanese   Presentation type：Poster presentation  

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

researchmap

Language：English   Presentation type：Poster presentation  

researchmap