Updated on 2021/12/20

写真a

 
SUGIMOTO Yukio
 
Organization
Medicine, Dentistry and Pharmaceutical Sciences Associate Professor
Position
Associate Professor
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Degree

  • 博士(薬学) ( 岡山大学 )

  • Doctor (Pharmaceutical Sciences) ( Okayama University )

Research Interests

  • ヒスタミン

  • アレルギー

  • Histamine

  • Allergy

Research Areas

  • Life Science / Immunology

  • Life Science / Pharmacology

  • Life Science / Pharmacology

  • Life Science / Pharmaceutical hygiene and biochemistry

Education

  • Okayama University   薬学研究科  

    - 1988

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    Country: Japan

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  • Okayama University    

    - 1988

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  • Okayama University    

    - 1986

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  • Okayama University   薬学部   製薬化

    - 1986

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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 准教授

    2004

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

    2004

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Professional Memberships

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Committee Memberships

  • 日本薬学会   ファルマシア 連絡委員  

    2015   

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    Committee type:Academic society

    日本薬学会

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  • 日本薬学会   ファルマシア トピックス専門小委員  

    2009 - 2011   

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    Committee type:Academic society

    日本薬学会

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  • 日本薬理学会   学術評議員  

    1999   

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    Committee type:Academic society

    日本薬理学会

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Papers

  • Analgesic agents without gastric damage: Design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors (vol 15, pg 1014, 2007) Reviewed

    Zheng Xiaoxia, Oda Hiroyuki, Takamatsu Kayo, Sugimoto Yukio, Tai Akihiro, Akaho Eiichi, Ali Hamed Ismail, Oshiki Toshiyuki, Kakuta Hiroki, Sasaki Kenji

    BIOORGANIC & MEDICINAL CHEMISTRY   15 ( 9 )   3299 - 3300   2007.5

  • Sequential analysis of histamine release and intracellular Ca2+ release from murine mast cells

    Kenji Tasaka, Yukio Sugimoto, Mitsunobu Mio

    International Archives of Allergy and Immunology   91 ( 2 )   211 - 213   1990

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    Publishing type:Research paper (scientific journal)  

    Stimulation of murine peritoneal mast cells with compound 48/80 at a concentration of 1 ug/ml elicited rather slow histamine release; the onset of release was observed 5 s after stimulation, and it reached a plateau at about 60 s. Both inositol-1, 4, 5-trisphosphate (IP3) and inositol-1, 4s-bisphosphate (IP2) contents increased to their maximum 5 s after stimulation. The IP3 content decreased to the control level more rapidly than that of IP2. Changes in the intracellular Ca2+ concentration of the quin 2 loaded mast cells were determined using a video-intensified microscopy system. The fluorescence intensity due to Ca-quin 2 complex increased rapidly after 48/80 stimulation in a Ca-free medium and reached the maximum at about 6-7 s. It became clear that the increase in IP3 content and the resulting Ca2+ release from the intracellular Ca store precede histamine release from murine mast cells. © 1990 S. Karger AG, Basel.

    DOI: 10.1159/000235118

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Books

  • FOOD STYLE 21

    杉本 幸雄( Role: Contributor ,  特集 食品由来成分によるアレルギー対策)

    食品化学新聞社  2019.11 

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  • 小児科 特集 アレルギー疾患におけるステロイド薬の局所療法-作用メカニズムと使い方

    金原出版株式会社  2016 

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  • Pediatrics of Japan

    2016 

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  • 肥満細胞の臨床

    先端医学社  2001 

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MISC

  • Involvement of glucocorticoid receptor activation on anti-inflammatory effect induced by peroxisome proliferator-activated receptor gamma agonist in mice

    Atsuki Yamamoto, Hiroki Kakuta, Yukio Sugimoto

    INTERNATIONAL IMMUNOPHARMACOLOGY   22 ( 1 )   204 - 208   2014.9

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    Language:English   Publisher:ELSEVIER SCIENCE BV  

    Glucocorticoids are effective anti-inflammatory agents widely used for the treatment of acute and chronic inflammatory diseases. Recent in vitro studies have proposed that glucocorticoid receptor (GR) activation is involved in peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist-induced effects. In this study, to examine the involvement of the GR in PPAR gamma agonist- and retinoid X receptor (RXR) agonist-mediated anti-inflammatory effects in vivo, we tested the anti-inflammatory effects of dexamethasone (a GR agonist) with pioglitazone (a PPAR gamma agonist) or 64N-ethyl-N-(3-isopropoxy-4-isopropylphenyl)-amino] nicotinic acid (NEt-3IP; an RXR agonist) by using an experimental model of carrageenan-induced inflammation. We also evaluated the effects of a GR antagonist on PPAR gamma agonist- or RXR agonist-induced anti-inflammatory effects. Results showed that the GR antagonist RU486 reduced the anti-inflammatory effects of GR or PPAR gamma agonists but not those of the RXR agonist In addition, combinations of GR and PPAR gamma agonists or GR and RXR agonists had no effect on carrageenan-induced paw edema. Moreover, the PPAR gamma antagonist GW9662 and RXR antagonist 6-[N-4-(trifluoromethyp-benzenesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-aminol nicotinic acid (NS-4TF) had no effect on the anti-inflammatory effect of the GR agonist dexamethasone. Therefore, it is suggested that GR activation in vivo does not play a direct role in PPAR gamma/RXR heterodimer signaling. In contrast, pioglitazone showed a partial anti-inflammatory effect via GR activation. These data provide evidence for the pro-inflammatory activity of pioglitazone. (C) 2014 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.intimp.2014.06.028

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  • Genomic and non-genomic effects of glucocorticoids on allergic rhinitis model in mice

    Eriko Kusaka, Mayu Sugiyama, None Senoo, Atsuki Yamamoto, Yukio Sugimoto

    INTERNATIONAL IMMUNOPHARMACOLOGY   16 ( 2 )   279 - 287   2013.6

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    Language:English   Publisher:ELSEVIER SCIENCE BV  

    Glucocorticoids (GCs) are well known for their anti-inflammatory effects, which are elicited through a transcriptional mechanism via a cytosolic glucocorticoid receptor (cGR)-mediated genomic effect. However, recent in vitro studies report that GCs can act as a membrane glucocorticoid receptor (mGR). This study aimed to examine whether mometasone furoate (MF) influences the nasal symptoms induced by histamine, substance P, ATP. Furthermore, the influences of various compounds on MF action were studied in vivo. The mice were intranasally administered with nasal symptom-inciting agents, and the occurrences of sneezing and nasal rubbing were counted. MF repressed the nasal symptoms caused when it was administered 10, 30 and 60 min before the induction of nasal symptoms. The repressive effect observed 10 min after the administration of MF was inhibited by RU486, a GR antagonist but not by actinomycin D, a transcriptional inhibitor. In contrast, the repressive effect observed 60 min after the administration of MF was inhibited by RU486 and actinomycin D. Therefore, the effects observed 10 and 60 min after the MF administration were classified as non-genomic and genomic effects, respectively. The non-genomic effect suppressed the nasal symptoms induced by m-3M3FBS, a phospholipase C (PLC) activator, and was inhibited by U-73122, a PLC inhibitor. The genomic effect was inhibited by N-(p-amylcinnamoyl) anthranilic acid, a phospholipase A(2) (PLA(2)) inhibitor. These results indicate that MF has a non-genomic effect through repression of the activation of PLC via the mGR, and MF has also a genomic effect that was influenced by the inhibition of PLA(2) through transcriptional regulation via cGR. (c) 2013 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.intimp.2013.03.030

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  • In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A

    Hidekazu Ishimoto, Mari Shibata, Yuki Myojin, Hideyuki Ito, Yukio Sugimoto, Akihiro Tai, Tsutomu Hatano

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   21 ( 19 )   5901 - 5904   2011.10

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    Language:English   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    Urolithin A is a major metabolite produced by rats and humans after consumption of pomegranate juice or pure ellagitannin geraniin. In this study, we investigated the anti-inflammatory effect of urolithin A on carrageenan-induced paw edema in mice. The volume of paw edema was reduced at 1 h after oral administration of urolithin A. In addition, plasma in treated mice exhibited significant oxygen radical antioxidant capacity (ORAC) scores with high plasma levels of the unconjugated form at 1 h after oral administration of urolithin A. These results indicate strong associations among plasma urolithin A levels, the plasma ORAC scores, and anti-inflammatory effects and may help explain a mechanism by which ellagitannins confer protection against inflammatory diseases. (C) 2011 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2011.07.086

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  • Prophylactic Effects of the Histamine H-1 Receptor Antagonist Epinastine and the Dual Thromboxane A(2) Receptor and Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells Antagonist Ramatroban on Allergic Rhinitis Model in Mice

    Yuh Suzuki, Toshio Inoue, Atsuki Yamamoto, Yukio Sugimoto

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   34 ( 4 )   507 - 510   2011.4

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    Language:English   Publisher:PHARMACEUTICAL SOC JAPAN  

    The prophylactic use of anti-allergic drugs has been proposed to be effective in the treatment of seasonal allergic rhinitis in humans. However, there is little information regarding the prophylactic effect of thromboxane A(2) (TXA(2)) receptor antagonist on allergic rhinitis. Recent studies revealed that a TXA(2) receptor antagonist ramatroban could block the prostaglandin D-2 (PGD(2)) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). In the present study, we investigated the prophylactic effects of the histamine H, receptor antagonist epinastine and the TXA(2) receptor antagonist ramatroban and seratrodast on mouse models of allergic rhinitis. Female BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin and alum on days 0, 5, 14 and 21. Seven days later, mice were sensitized by intranasal application of ovalbumin thrice a week. Drugs were administered once a day from day 22. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms (sneezing and nasal rubbing). Histamine sensitivity and eosinophil infiltration into the nasal mucosa were also determined. Epinastine and ramatroban significantly reduced nasal symptoms and the number of eosinophils in the nasal mucosa. Seratrodast showed no effect on nasal symptoms and cosinophil infiltration into the nasal mucosa. In addition, histamine sensitivity was reduced by epinastine and ramatroban. These results indicate that epinastine and ramatroban induce the prophylactic effect on allergic rhinitis.

    DOI: 10.1248/bpb.34.507

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  • Involvement of the Retinoid X Receptor Ligand in the Anti-Inflammatory Effect Induced by Peroxisome Proliferator-Activated Receptor gamma Agonist In Vivo

    Atsuki Yamamoto, Hiroki Kakuta, Hiroyuki Miyachi, Yukio Sugimoto

    PPAR RESEARCH   2011 ( 840194 )   1 - 8   2011

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    Language:English   Publisher:HINDAWI PUBLISHING CORPORATION  

    Peroxisome proliferator-activated receptor gamma (PPAR gamma) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPAR gamma agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPAR gamma-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPAR gamma agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPAR antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPAR gamma agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPAR gamma antagonist. PPAR gamma agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPAR gamma agonist-induced anti-inflammatory effect.

    DOI: 10.1155/2011/840194

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  • Involvement of peripheral mu opioid receptors in scratching behavior in mice

    Atsuki Yamamoto, Yukio Sugimoto

    EUROPEAN JOURNAL OF PHARMACOLOGY   649 ( 1-3 )   336 - 341   2010.12

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    Pruritus is a common adverse effect of mid treatment However the mechanism by which pruritus is induced by opioid administration is unclear In this study we examined the effects of the intradermal injection of loperamide a peripherally restricted plaid receptor agonist on the itch sensation When injected intradermally into the rostral part of the back in mice loperamide elicited scratching behavior We also examined the effects of the selective mu opioid receptor agonist [d-Ala(2) N-Me-Phe(4) Gly(5)-ol]-enkephalin acetate (DAMGO) the selective delta opioid receptor agonist [d-Pen(2 5)]-enkephalin (DPDPE) and the selective kappa opioid receptor agonist U-50488H on scratching behavior in mice in order to determine which subtype is involved in opioid-induced pruritus Following intradermal injection into the rostral part of the back in mice DAMGO elicited scratching behavior while DPDPE and U 50488H did not This suggests that peripheral mu opioid activation elicits the itch sensation Next, we focused on the treatment of opioid-induced itch sensation without central adverse effects Naloxone methiodide is a peripherally restricted opioid receptor antagonist In the present study naloxone methiodide significantly suppressed scratching behavior induced by loperamide and DAMGO These findings suggest that mu opioid receptors play a primary role in peripheral pruritus and that naloxone methiodide may represent a possible remedy for opioid-induced itching (C) 2010 Elsevier B V All rights reserved

    DOI: 10.1016/j.ejphar.2010.07.039

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  • Effect of 5-aminosalicylate on allergic rhinitis model in mice

    Shoji Kuyama, Atsuki Yamamoto, Mayu Sugiyama, Hiroki Kakuta, Yukio Sugimoto

    INTERNATIONAL IMMUNOPHARMACOLOGY   10 ( 6 )   713 - 716   2010.6

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    Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in allergic rhinitis. It has been reported that 5-aminosalicylate (5-ASA) has an affinity for PPAR gamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL)-4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA-specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis. (C) 2010 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.intimp.2010.03.007

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  • 新規低脂溶性RARβ選択的アゴニストの創製研究

    大澤 史宜, 山田 翔也, 山本 篤毅, 深井 良祐, 鄭 霞暁, 槇島 誠, 杉本 幸雄, 田井 章博, 加来田 博貴

    日本薬学会年会要旨集   130年会 ( 2 )   243 - 243   2010.3

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  • NOの被観血的、非侵襲的な定量法の開発とアレルギーモデルでの検証

    高島 征助, 妹尾 訓枝, 山本 篤毅, 杉本 幸雄, 加来田 博貴

    日本薬学会年会要旨集   130年会 ( 3 )   138 - 138   2010.3

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  • Pioglitazoneの抗炎症作用における作用機序に関する研究

    山本 篤毅, 杉山 茉由, 妹尾 訓枝, 日下 絵梨子, 篠崎 亮介, 加来田 博貴, 杉本 幸雄

    日本薬理学雑誌   135 ( 3 )   21P - 21P   2010.3

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  • 核内受容体RXRアゴニストのマウス鼻アレルギーモデルに対する効果について

    杉山 茉由, 山本 篤毅, 篠崎 亮介, 日下 絵梨子, 妹尾 訓枝, 宮地 弘幸, 加来田 博貴, 杉本 幸雄

    日本薬理学雑誌   135 ( 3 )   21P - 21P   2010.3

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  • Characterization of scratching behavior induced by intradermal administration of morphine and fentanyl in mice

    Atsuki Yamamoto, Shoji Kuyama, Chiaki Kamei, Yukio Sugimoto

    EUROPEAN JOURNAL OF PHARMACOLOGY   627 ( 1-3 )   162 - 166   2010.2

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    Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. When injected intradermally into the rostral back of mice, morphine and fentanyl elicited scratching behavior. in addition, an opioid receptor antagonist, naloxone, and a peripherally restricted opioid receptor antagonist, naloxone methiodide, significantly suppressed morphine- and fentanyl-induced scratching behavior. Moreover, the morphine-induced scratching behavior was suppressed by histamine H(1) receptor antagonists, such as diphenhydramine, chlorpheniramine, epinastine and cetirizine. On the other hand, fentanyl-induced scratching behavior was not suppressed by histamine H(1) receptor antagonists. Additionally, scratching behavior induced by morphine and fentanyl were not suppressed by glucocorticoids (predonisolone and dexamethasone). In conclusion, opioid-induced itching may involve in peripheral opioid receptors. Moreover, histamine and arachidonic acid metabolites played no main role in opioid-induced scratching behavior. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ejphar.2009.10.066

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  • カラゲニン浮腫試験に対するRXRアゴニストNEt-3IPの効果

    山本 篤毅, 杉山 茉由, 篠崎 亮介, 宮地 弘幸, 加来田 博貴, 杉本 幸雄

    日本薬理学雑誌   134 ( 4 )   11P - 11P   2009.10

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  • 核内受容体RXRアゴニストの抗アレルギー作用について

    杉山 茉由, 山本 篤毅, 篠崎 亮介, 宮地 弘幸, 加来田 博貴, 杉本 幸雄

    日本薬理学雑誌   134 ( 4 )   10P - 10P   2009.10

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  • RXRアゴニストNEt-3IPの抗アレルギー作用について

    加来田 博貴, 久山 翔司, 尾崎 友美, 杉山 茉由, 宇野 茂之, 槇島 誠, 森下 健一, 鄭 暁霞, 原田 隼, 杉本 幸雄

    日本薬学会年会要旨集   129年会 ( 2 )   114 - 114   2009.3

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  • Effect of the Oral Absorption Benzenesulfonanilide-Type Cyclooxygenase-1 Inhibitors on Analgesic Action and Gastric Ulcer Formation

    Xiaoxia Zheng, Hiroyuki Oda, Shun Harada, Yukio Sugimoto, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

    JOURNAL OF PHARMACEUTICAL SCIENCES   97 ( 12 )   5446 - 5452   2008.12

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    Language:English   Publisher:JOHN WILEY & SONS INC  

    A benzensulfonanilide-type cyclooxygenase-1 (COX-1)-selective inhibitor, ZXX2-77: 4-amino-4'-chloro-N-methylbenzenesulfonanilide (4a), has been reported as a novel analgesic that does not cause gastric damage. This compound has a weak analgesic effect but has potent in vitro COX-1 inhibitory activity. Since the reason for the weak analgesic effect in vivo was thought to be the low rate of oral absorption, the blood concentration of ZXX2-77 (4a) was measured in rats. It was found that the C(max) value (1.2 mu M) of ZXX2-77 (4a) at a dose of 30 mg/kg did not reach the COX-1 IC(50) value (3.2 mu M). On the other hand, ZXX2-79 (4b) (SO(2)NH derivative of ZXX2-77 (4a); 4-amino-4'-chlorobenzenesulfonanilide), which shows less potent COX inhibitory activities (COX-1 IC(50) = 12 mu M, COX-2 IC(50) = 150 mu M) than those of ZXX2-77 (4a) in vitro, was found to be more absorbable (C(max) - 16 mu M at a dose of 30 mg/kg in rats) than ZXX2-77 (4a). Furthermore, ZXX2-79 (4b) not only showed a potent analgesic effect in a formalin test but also caused little gastric damage. These findings indicate that demethylated sulfonamide compounds are more easily absorbed than are N-methylated sulfonamide compounds and suggest that COX-1-selective inhibitors will be useful as analgesics that do not cause gastric damage. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5446-5452, 2008

    DOI: 10.1002/jps.21388

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  • Participation of Histamine H(3) Receptors in Experimental Allergic Rhinitis of Mice

    Emiko Yokota, Shoji Kuyama, Yukio Sugimoto, Masami Ogawa, Chiaki Kamei

    JOURNAL OF PHARMACOLOGICAL SCIENCES   108 ( 2 )   206 - 211   2008.10

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    The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.

    DOI: 10.1254/jphs.08164FP

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  • シクロオキシゲナーゼ1阻害剤は胃潰瘍形成のない魅力的な抗がん剤候補である。ベンズアミドタイプのCOX-1阻害剤による提示。(COX-1-selective inhibitors are attractive candidates for anti-cancer agents that do not cause gastric damage)

    加来田 博貴, 鄭 曉霞, 小田 博之, 原田 隼, 杉本 幸雄, 永澤 秀子, 佐々木 健二, 田井 章博

    日本癌学会総会記事   67回   369 - 369   2008.9

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  • Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor

    Hiroki Kakuta, Xiaoxia Zheng, Hiroyuki Oda, Shun Harada, Yukio Sugimoto, Kenji Sasaki, Akihiro Tai

    JOURNAL OF MEDICINAL CHEMISTRY   51 ( 8 )   2400 - 2411   2008.4

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    Language:English   Publisher:AMER CHEMICAL SOC  

    Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1IC(50) = 0.80 +/- 0.05 mu M, COX-2IC(50) = 210 I mu M). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

    DOI: 10.1021/jm701191z

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  • 新規シクロオキシゲナーゼ1(COX-1)阻害剤の開発とその胃潰瘍形成の有無および鎮痛効果の検証

    加来田 博貴, 鄭 暁霞, 小田 博之, 原田 隼, 大澤 史宜, 藤井 周司, 永澤 秀子, アリ・ハメッド, 赤穂 榮一, 佐々木 健二, 杉本 幸雄, 田井 章博

    日本薬学会年会要旨集   128年会 ( 2 )   51 - 51   2008.3

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  • RXRα/βデュアルアゴニストNEt-3IPの開発と生理活性評価

    高松 佳代, 高野 敦史, 薬師寺 信匡, 師橋 一徳, 森下 健一, 大澤 史宜, 藤井 周司, 松浦 信康, 槇島 誠, 永澤 秀子, 杉本 幸雄, 田井 章博, 佐々木 健二, 加来田 博貴

    日本薬学会年会要旨集   128年会 ( 2 )   51 - 51   2008.3

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  • Analgesic agents without gastric damage: Design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors

    Xiaoxia Zheng, Hiroyuki Oda, Kayo Takamatsu, Yukio Sugimoto, Akihiro Tai, Eiichi Akaho, Hamed Ismail Ali, Toshiyuki Oshiki, Hiroki Kakuta, Kenji Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY   15 ( 2 )   1014 - 1021   2007.1

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    In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance. (c) 2006 Published by Elsevier Ltd.

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  • Prophylactic effects of antiallergic drugs on allergic rhinitis model in mice

    Yuh Suzuki, Yukio Sugimoto, Chiaki Kamei

    JOURNAL OF PHARMACOLOGICAL SCIENCES   103   161P - 161P   2007

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  • Effect of paroxetine on marble-burying behavior in mice

    K Shinomiya, Y Fujii, Y Sugimoto, N Azuma, S Tokunaga, K Kitazumi, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   27 ( 10 )   685 - 687   2005.12

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    The present study was undertaken to investigate the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI). on marble-burying behavior in mice in comparison with those of fluvoamine and clomipramine. Marble-burying test is extensively used as an animal model for obsessive/compulsive disorder A significant inhibition in marble-burying behavior was observed with paroxetine, at a dose of,10 mg/kg. The earlier SSRI, fluvoxamine, also significantly inhibited marble-burying behavior at a dose of 30 mg/kg. Although clomipramine. a tricyclic antidepressant, caused an inhibition in marble-burying behavior, a high dose of 100 mg/kg was needed to show a significant effect. On the other hand. all the drugs used in the present study showed no significant changes in spontaneous locomotor activity at doses inhibiting marble-burying behavior. In conclusion, it was confirnied that paroxetine has a potent inhibitory effect on marble-burying behavior in mice, and could have a similar antiobsessive/ anticompulsive activity in hunan beings. (c) 2005 Prous Science. All rights reserved.

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  • Pruritus-associated response mediated by cutaneous histamine H-3 receptors

    Y Sugimoto, Y Iba, Y Nakamura, R Kayasuga, C Kamei

    CLINICAL AND EXPERIMENTAL ALLERGY   34 ( 3 )   456 - 459   2004.3

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    Background Histamine is one of the most common chemical mediators causing pruritus, and H-1 receptor antagonists have been used as a first choice in its treatment. On the other hand, although the presence of H-3 receptors has been identified in the skin, few studies have investigated the involvement of H-3 receptors on pruritus.
    Objective The purpose of this study was to examine whether H-3 receptor agonist or antagonist influences the incidence of scratching behaviour in ICR or mast cell-deficient WBB6F(1)-W/W-V mice.
    Methods The mice were given an intradermal injection of H-3 receptor agonist or antagonist into the rostral part of the back, and the occurrence of scratching behaviour at the injected site by the hind paws was counted over 60 min.
    Results H-3 receptor antagonists, thioperamide and AQ0145 significantly increased the incidence of scratching behaviour in ICR mice. H-3 receptor agonist, (R)-alpha-methylhistamine, had no effect. On the other hand, (R)-alpha-methylhistamine significantly inhibited thioperamide or AQ0145-induced scratching behaviour. In addition, both thioperamide and AQ0145 elicited scratching behaviour in mast cell-deficient WBB6F(1)-W/W-V mice.
    Conclusion From these results, it may be concluded that H-3 receptors are involved in the modulation of pruritus in the skin, and mast cells are not essential in this response. In addition, H-3 receptor agonists can be useful as a novel therapeutic approach against pruritus.

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  • Histamine H-3 receptors regulate vascular permeability changes in the skin of mast cell-deficient mice

    MA Hossen, Y Fujii, Y Sugimoto, R Kayasuga, C Kamei

    INTERNATIONAL IMMUNOPHARMACOLOGY   3 ( 12 )   1563 - 1568   2003.11

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    The participation of histamine H-3 receptors in the regulation of skin vascular permeability changes in mast cell-deficient mice was studied. Although intradermal injection of histamine H-3 antagonists, iodophenpropit and clobenpropit, at a dose of 100 nmol/site caused significant increases in skin vascular permeability in both mast cell-deficient (WBB6F1 W/W-v) and wildtype (WBB6F1 +/+) mice, this response was significantly lower in mast cell-deficient mice than in the wild-type controls. Histamine also caused dose-related increases in skin vascular permeability in both wild-type and mast cell-deficient mice. Significant effects were observed at doses of 10 and 100 nmol/site, and no significant difference in skin vascular permeability was observed between mast cell-deficient and wild-type mice. However, histamine contents of dorsal skin in mast cell-deficient mice were significantly lower than in wild-type mice. In addition, the H, antagonists diphenhydramine and chlorpheniramine and the NK1 antagonists, L-732,13 8 and L-733,060, were able to antagonize H-3 antagonist-induced skin vascular permeability. These results indicated that blockade of H-3 receptors by H-3 antagonists induce skin vascular permeability through mast cell-dependent mechanisms. In addition, histamine and, to a lesser extent substance P are involved in the reaction. (C) 2003 Published by Elsevier B.V.

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  • Involvement of histamine H-3 receptors in scratching behaviour in mast cell-deficient mice

    MA Hossen, Y Sugimoto, R Kayasuga, C Kamei

    BRITISH JOURNAL OF DERMATOLOGY   149 ( 1 )   17 - 22   2003.7

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    Background Although the roles of histamine H-3 receptors have been studied in several tissues such as the brain, lung, spleen, colon and peripheral sensory nerve endings, the involvement of H-3 receptors in skin responses particularly in relation to scratching behaviour are not well documented.
    Objectives This work was performed to study the effects of histamine H-3 antagonists on scratching behaviour in mast cell-deficient mice.
    Methods Histamine H-3 antagonists iodophenpropit and clobenpropit, histamine and substance P were injected intradermally into the rostral part of the back of mast cell-deficient (WBB6F1 W/W-v ) and wild-type (WBB6F1+/+) mice and scratching behaviour was measured for 60 min. The effects of H-1 antagonists on scratching behaviour induced by H-3 antagonists were also investigated.
    Results Intradermal injection of iodophenpropit and clobenpropit at doses of 10 and 100 nmol per site caused significant increases in scratching behaviour in both mast cell-deficient and wild-type mice. Histamine also caused a dose-related increase in the incidence of scratching behaviour, and a significant effect was observed at a dose of 100 nmol per site in both mast cell-deficient and wild-type mice. Substance P was also effective in causing scratching behaviour in both mast cell-deficient and wild-type mice. However, histamine H-1 antagonists diphenhydramine and chlorphenamine failed to inhibit H-3 antagonist-induced scratching behaviour in both types of mice.
    Conclusions Our results indicated that intradermal injection of H-3 antagonists induces scratching behaviour and that chemical mediators other than histamine seem to be involved in the response.

    DOI: 10.1046/j.1365-2133.2003.05341.x

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  • Inhibitory effects of glucocorticoids on rat eosinophil superoxide generation and chemotaxis

    Y Sugimoto, M Ogawa, N Tai, C Kamei

    INTERNATIONAL IMMUNOPHARMACOLOGY   3 ( 6 )   845 - 852   2003.6

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    Eosinophil infiltration into inflammatory tissues and the subsequent release of inflammatory mediators are the hallmarks of several inflammatory allergic diseases. Although there have been a considerable number of publications on anti-inflammatory effects of glucocorticoids, little is known about whether glucocorticoids affect the activation of eosinophils directly. We studied the effects of three glucocorticoids, mometasone furoate, dexamethasone and beclomethasone dipropionate, on superoxide generation and the chemotaxis of rat eosinophils. Highly purified rat eosinophils were treated for 6 h with mometasone furoate, dexamethasone or beclomethasone dipropionate. Eosinophils were stimulated with phorbol myristate acetate (PMA) for superoxide generation, while for induction of chemotaxis, platelet-activating factor (PAF) or leukotriene B-4 (LTB4) was used. None of the glucocorticoids used in the present study caused significant suppressive effects on superoxide generation induced by PMA. On the other hand, both PAF- and LTB4-induced migration of rat eosinophils were inhibited in a concentration-dependent manner by glucocorticoids. Mometasone furoate showed a significant effect at concentrations higher than 10(-11) M. Dexamethasone and beclomethasone dipropionate also caused a significant inhibition at concentrations higher than 10(-8) and 10(-7) M, respectively These results indicated that the anti-inflammatory effects of glucocorticoids were mediated by direct inhibition of eosinophil migration. Furthermore, mometasone furoate was suggested to be more useful than the other drugs in the treatment of allergic diseases responsible for eosinophil chemotaxis. (C) 2003 Elsevier Science B.V. All rights reserved.

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  • Evaluation of the effects of anti-pruritic drugs on scratch responses using histamine H-1 receptor-deficient mice

    Y Sugimoto, Y Nakamura, MA Hossen, T Watanabe, C Kamei

    EUROPEAN JOURNAL OF PHARMACOLOGY   470 ( 1-2 )   113 - 116   2003.5

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    The effects of anti-pruritic drugs on scratching behavior associated with passive cutaneous anaphylaxis in histamine H-1 receptor-deficient and wild-type mice were studied. Passive sensitization with mouse monoclonal anti-dinitrophenyl-immunoglobulin E (IgE) resulted in an increase in the incidence of scratching behavior induced by intravenous injection of dinitrophenyl-ovalbumin in both wild-type and histamine H-1 receptor-deficient mice. The histamine H-1 receptor antagonist diphenhydramine inhibited scratching behavior induced by antigen in passively sensitized wild-type mice, whereas no effect was observed in histamine H-1 receptor-deficient mice. On the other hand, oxatomide inhibited scratching behavior in both mice, although the effect in wild-type mice was more potent than that in histamine H-1 receptor-deficient mice. Tranilast inhibited scratching behavior with the same potency in both mice. We concluded that the scratching behavior associated with passive cutaneous anaphylaxis involves not only histamine H-1 receptors but also other chemical mediators. Furthermore, the results of the present study indicated that oxatomide has an antagonistic effect on histamine H-1 receptors as well as anti-pruritic effect in vivo. (C) 2003 Elsevier Science B.V All rights reserved.

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  • Effects of [Arg(8)]-vasopressin on regional cerebral blood flow in spontaneously hypertensive rats

    A Azuma, Y Sugimoto, M Mio, K Shinomiya, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   25 ( 3 )   193 - 197   2003.4

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    The effects of [Arg(8)]-vasopressin (AVP) and related compounds on regional cerebral blood flow (rCBF) in the hippocampus were studied using conscious spontaneously hypertensive rats (SHR). rCBF in the hippocampus decreased gradually with age in proportion to an increase in mean blood pressure. Subcutaneous injection of AVP caused a dose-dependent increase in rCBF in the hippocamous. The effects of the metabolic fragments AVP4-9 and A VP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V-2 antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V-2 agonist, increased rCBF in the hippocampus. On the other hand, the AVP-induced increase in rCBF in the hippocampus was not antagonized by OPC-21268, a vasopressin V-1 antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site. (C) 2003 Prous Science. All rights reserved.

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  • Possible role of mucosal mast cells in the recovery process of colitis induced by dextran sulfate sodium in rats

    Y Iba, Y Sugimoto, C Kamei, T Masukawa

    INTERNATIONAL IMMUNOPHARMACOLOGY   3 ( 4 )   485 - 491   2003.4

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    To clarify the role of mucosal mast cells in the lesion sites of colitis induced by dextran sulfate sodium (DSS) in rats, we investigated the histological changes and alterations relevant to mucosal mast cells in the spontaneous recovery process of colitis. Oral administration of 4% DSS solution for 11 days resulted in surface epithelial loss, crypt loss and goblet cell depletion in the rectal mucosa. A marked infiltration of inflammatory cells into the mucosa, which was consistent with a significant increase in myeloperoxidase (MPO) activity, was observed. In addition, mucosal mast cell number and rat mast cell protease (RMCP) I and H levels in the rectum increased at day 0 after DSS treatment, and most of the mucosal mast cells were degranulated. After replacing 4% DSS solution with water, re-epithelialization and restoration of goblet cells were observed at day 5 and day 10, respectively, but crypt damage was hardly recovered even at day 20. The elevated myeloperoxidase activity was significantly decreased from day 5 after DSS treatment. The increased number of mucosal mast cells was further elevated up to about 1.5-fold at day 10 and day 20 after DSS treatment and little degranulation was observed. In the spontaneous recovery process, the increased rat mast cell protease H level in the rectum was maintained for 20 days, while the increased rat mast cell protease I level was gradually decreased and recovered to control level. These results suggest that proliferated mucosal mast cells remained for 20 days, although most of infiltrated inflammatory cells disappeared in spontaneous recovery process of colitis. It may therefore be presumed that proliferated mucosal mast cells play a role in spontaneous recovery process of the colitis induced by DSS. (C) 2003 Elsevier Science B.V. All rights reserved.

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  • Inhibitory effects of propolis granular A. P. C on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice

    Y Sugimoto, Y Iba, R Kayasuga, Y Kirino, M Nishiga, MA Hossen, K Okihara, H Sugimoto, H Yamada, C Kamei

    CANCER LETTERS   193 ( 2 )   155 - 159   2003.4

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    We examined the effect of propolis granular A. P. C on lung tumorigenesis in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6 days/week from I week before NNK administration and throughout the experiment. Sixteen weeks after the NNK treatment, the mice were killed and the number of surface lung tumors was measured. The number of lung tumors in mice treated with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that observed in control mice. Propolis granular A. P. C significantly decreased the number of lung tumors induced by NNK. These results indicate that propolis granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis in mice. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

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  • Effects of NMDA antagonist MK-801 on radial maze performance in Zucker rats

    M Nishiga, Y Fujii, Y Sugimoto, M Konishi, C Kamei

    BRAIN RESEARCH   950 ( 1-2 )   127 - 129   2002.9

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    We examined the participation of the NMDA receptor in the histaminergic system using radial maze performance in Zucker rats. Although pyrilamine caused a significant effect on spatial memory deficit in lean rats, no significant spatial memory deficit was observed in obese rats. On the other hand, MK-801 caused significant spatial memory deficits in obese rats in comparison with lean rats. These results indicate that the histaminergic neuron is not closely related with the radial maze performance in obese rats. In addition, the potent effect of MK-801 observed in obese rats compared with lean rats may be responsible for the activation of NMDA receptors in obese rats. (C) 2002 Elsevier Science B.V. All rights reserved.

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  • Effect of docosahexaenoic acid-fortified Chlorella vulgaris strain CK22 on the radial maze performance in aged mice

    Y Sugimoto, C Taga, M Nishiga, M Fujwara, F Konishi, K Tanaka, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   25 ( 8 )   1090 - 1092   2002.8

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    Effect of docosahexaenoic acid (DHA) [22:6(n-3)]-fortified Chlorella oil fraction on radial maze performance was studied in aged mice. Male ICR mice aged 9 months were fed a diet containing 2 g DHA-fortified Chlorella oil fraction/100 g diet or normal diet (Control group) for 2 months. Two months after the start of feeding, the mice were tested for learning ability related to 2 types of memory, reference memory and working memory, with the partially (4 of 8) baited eight-arm radial maze. Reference memory is a kind of information that should be retained until the next trial. Working memory is a kind of information that disappears in a short time. Entry into the unbaited arms and repeated entry into the visited arms were defined as reference memory errors and working memory errors, respectively. DHA-fortified Chlorella oil fraction administration to mice for 2 months resulted in a significant decrease in the number of working memory errors without affecting the number of reference memory errors. A significant increase in the DHA content in the brain was also observed. These results suggest that the intake of DHA-fortified Chlorella oil fraction effectively enhances working memory in maze performance.

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  • Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H-1 receptors

    R Kayasuga, Y Sugimoto, T Watanabe, C Kamei

    EUROPEAN JOURNAL OF PHARMACOLOGY   449 ( 3 )   287 - 291   2002.8

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    The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H-1 receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H-1 receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H-1 receptor-deficient mice. Histamine H-1 receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H-1 receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H-1 receptors and thromboxane A(2) receptors were involved in the responses. (C) 2002 Elsevier Science B.V. All rights reserved.

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  • Changes in membrane potential induced by compound 48/80 in the peritoneal mast cells of rats

    Y Nakayama, M Mio, Y Sugimoto, Y Fujii, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   24 ( 5 )   267 - 273   2002.6

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    The changes in membrane potential induced by, compound 48/80 were studied using rat peritoneal mast cells, The mean resting membrane potential of rat mast cells was -12.3 +/- 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked-depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K+-pump, respectively. (C) 2002 Prous Science. All rights reserved.

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  • Histamine H-1 receptors are involved in mouse nasal allergic responses: a demonstration with H-1 receptor-deficient mice

    R Kayasuga, Y Sugimoto, T Watanabe, C Kamei

    INTERNATIONAL IMMUNOPHARMACOLOGY   2 ( 6 )   745 - 750   2002.5

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    The role of histamine H-1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H-1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H-1 receptor-deficient mice. The histamine H-1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent manner in wild-type mice, but no such increase was fund in histamine H, receptor-deficient mice. On the other hand, the histamine H-2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H-1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H-2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H, receptors play an important role in nasal allergy symptoms induced by histamine. (C) 2002 Elsevier Science B.V All rights reserved.

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  • Effects of the NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats

    M Nishiga, Y Sugimoto, C Taga, Y Fujii, C Kamei

    LIFE SCIENCES   70 ( 18 )   2199 - 2208   2002.3

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    We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-ann radial maze in rats. A significant decrease in histamine content in the hippocampus was observed after long-term feeding of rats with a histidine-deficient diet. At the same time, significant enhancement of the acquisition process in radial maze performance was also observed. Pyrilamine did not show a significant effect on radial maze performance in histidine-deficient rats. On the other hand, pyrilamine caused a significant spatial memory deficit in control rats. Scopolamine was effective in inhibiting spatial memory in both histidine-deficient and control rats. MK-801 caused spatial memory deficits more potently in histidine-deficient rats than in controls. Brain glycine contents showed a significant increase in the hippocampus in histidine-deficient rats. These results indicated that the spatial memory deficits induced by MK-801 in histidine-deficient rats are closely related to increased glycine levels and activation of NMDA receptors. (C) 2002 Elsevier Science Inc. All rights reserved.

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  • Antiallergic effect of flavonoid glycosides obtained from Mentha piperita L.

    T Inoue, Y Sugimoto, H Masuda, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   25 ( 2 )   256 - 259   2002.2

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    Six flavonoid glycosides, eriocitrin (1), narirutin (2), hesperidin (3), luteolin-7-O-rutinoside (4), isorhoifolin (5), diosmin (6), rosmarinic acid (7) and 5,7-dihydroxycromone-7-O-rutinoside (8), were isolated from the aerial part of Mentha piperita L. Among these compounds, compound 4 showed a potent inhibitory effect on histamine release induced by compound 48/80 and antigen-antibody reaction. This compound was more effective than luteolin and luteolin-7-O-glucoside in inhibiting histamine release from rat peritoneal mast cells. Compound 4 also caused a dose-related inhibition of the antigen-induced nasal response and significant effects were observed at doses of 100 and 300 mg/kg. These results indicate that compound 4 may be clinically useful in alleviating the nasal symptoms of allergic rhinitis.

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  • Participation of mast cells in colitis inflammation induced by dextran sulfate sodium

    Y Iba, Y Sugimoto, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   24 ( 1 )   15 - 18   2002.1

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    We investigated the participation of mast cells in colitis inflammation induced by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO) activity were measured to confirm the occurrence of colitis. Rat mast cell protease (RMPCP) II levels in the serum were estimated as an index of mast cell degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), respectively. Administration of 4% DSS resulted in time-related increases in damage score. MPO activity and serum RMCP II levels, which were statistically significant at 7 and 11 days after treatment. Tissue RMCP I and RMCP II levels in the rectum were also increased significantly at 7 and 11 days, and 11 days, respectively after free drinking of 4% DSS. These results suggested that mast cells proliferated or the amount of protease per mast cell increased in the sites of inflammation induced by DSS, and that these mast cells may modulate the disorders observed in DSS-induced colitis. (C) 2002 Prous Science. All rights reserved.

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  • Effect of levocabastine hydrochloride on allergic conjunctivitis in rats

    19 ( 6 )   787 - 791   2002

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  • ラットのアレルギー性結膜炎に対する塩酸レボカバスチンの効果

    Kazuhisa Minami, Yukio Sugimoto, Chiaki Kamei

    J. Eye   19 ( 6 )   787 - 791   2002

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  • Effects of histidine on working memory deficits induced by the 5-HT1A-receptor agonist 8-OH-DPAT

    S Isayama, Y Sugimoto, M Nishiga, C Kamei

    JAPANESE JOURNAL OF PHARMACOLOGY   86 ( 4 )   451 - 453   2001.8

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    We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetratin (8-OH-DPAT). Working memory deficits were elicited by 8-OH-DPAT without affecting reference memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at doses causing a significant increase in brain histamine content. This finding suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory deficit.

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  • Effects of vasopressin on histamine H-1 receptor antagonist-induced spatial memory deficits in rats

    C Taga, Y Sugimoto, M Nishiga, Y Fujii, C Kamei

    EUROPEAN JOURNAL OF PHARMACOLOGY   423 ( 2-3 )   167 - 170   2001.7

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    The effects of [Arg(8)] vasopressin on histamine H-1 receptor antagonist-induced memory deficits were investigated using the eight-arm radial maize performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increaser in the number of total errors, reference memory errors and working memory errors. [Arg(8)] vasopressin improved not only scopolamine-but also pyrilamine-and diphenhydramine-induced memory deficits, although a high dose of [Arg(8)] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg(8)] vasopressin content were studied, and the hippocampus [Arg(8)] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg(8)] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory. (C) 2001 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0014-2999(01)01080-9

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  • Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats

    T Inoue, Y Sugimoto, H Masuda, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   24 ( 1 )   92 - 95   2001.1

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    The present study,vas carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 mug/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 mug/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively: Furthermore, the 50% EtOH eluate inhibited die leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.

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  • Involvement of mast cells on ulcerative colitis model in rats

    22 ( Suppl. 1 )   S144-S150   2001

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  • ラット潰瘍性大腸炎モデルにおける肥満細胞の関与

    杉本幸雄, 亀井千晃

    Ther. Res.   22 ( Suppl. 1 )   S144-S150   2001

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  • Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats

    C Kamei, M Ohuchi, Y Sugimoto, C Okuma

    BRAIN RESEARCH   887 ( 1 )   183 - 186   2000.12

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    In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0006-8993(00)03041-9

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  • Vascular permeability in allergic conjunctivitis in mice lacking histamine H-1 receptors

    H Nakahara, K Izushi, Y Sugimoto, T Watanabe, C Kamei

    EUROPEAN JOURNAL OF PHARMACOLOGY   409 ( 3 )   313 - 317   2000.12

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    To clarify the role of histamine H-1 receptors in allergic conjunctivitis, changes in vascular permeability of the conjunctiva were measured in histamine H-1 receptor deficient mice. Wild-type mice showed a significant increase in vascular permeability of the conjunctiva induced by histamine. However, no such increase was found in histamine H-1 receptor deficient mice. On the other hand, no differences were observed between wild-type and histamine H-1 receptor deficient mice in response to serotonin. A significant increase in vascular permeability was observed in actively sensitized wild-type mice, whereas no increase was observed in histamine H-1 receptor deficient mice. Similar findings were noted in passively sensitized animals. Histamine contents of the conjunctiva were significantly decreased by topical application of antigen in both wild-type and histamine H-1 receptor deficient mice after active sensitization with antigen. These findings suggested that vascular permeability in the conjunctiva in allergic conjunctivitis is entirely regulated through histamine H-1 receptor. (C) 2000 Elsevier Science B.V. All rights reserved.

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  • Effects of Fujibitol, a remedy for nasal symptoms, on experimental allergic rhinitis in rats

    M Kakimoto, Y Sugimoto, M Harada, Y Kobayashi, C Okuma, C Taga, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   23 ( 9 )   1055 - 1058   2000.9

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    The effects of Fujibitol, a preparation of crude drugs in wide clinical use for treatment of chronic rhinitis and empyema, on experimental allergic rhinitis in rats were studied. Fujibitol inhibited nasal allergic symptoms, Le. sneezing and nasal rubbing, induced by antigen in sensitized animals. An increase in dye leakage into the nasal cavity induced by antigen was also inhibited by Fujibitol. On the other hand, no inhibitory effects were observed on either the nasal allergic symptoms or increase in dye leakage into the nasal cavity induced by histamine. However, Fujibitol was effective in inhibiting histamine release from the nasal cavity induced by antigen. Oxatomide used as positive control drug showed potent inhibitory effects on nasal symptoms and dye leakage into the nasal cavity induced by histamine and antigen. These results suggested that Fujibitol showed a remarkable protective effect against experimental rhinitis induced by antigen via inhibition of histamine release from the nasal cavity.

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  • Influences of everninomicin, vancomycin and teicoplanin on chemical mediator release from rat peritoneal mast cells

    Y Sugimoto, Y Iba, K Utsugi, C Kamei

    JAPANESE JOURNAL OF PHARMACOLOGY   83 ( 4 )   300 - 305   2000.8

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    We examined influences of certain antibiotics on the release of chemical mediators from isolated rat peritoneal mast cells in vitro. Isolated peritoneal mast cells were obtained from male Wistar strain rats. Everninomicin (0.06 - 1.2 mg/ml), vancomycin (0.05 - 1.0 mg/ml), teicoplanin (0.07 - 1.4 mg/ml) and concanavalin A (0.01 mg/ml) were used. Isolated mast cells were incubated in the presence of various concentrations of the test compound at 37 degrees C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D-2 (PGD(2)) contents of the supernatant were determined by enzyme immunoassay. Everninomicin (0.06-1.2 mg/ml) had no influence on histamine and PGD2 release from mast cells. On the other hand, vancomycin significantly released both histamine (0.5 and 1.0 mg/ml) and PGD(2) (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD(2) release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD(2) release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD:! release. These results suggest that everninomicin causes no chemical mediator release from mast cells, different from vancomycin and teicoplanin.

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  • A new model of allergic rhinitis in rats by topical sensitization and evaluation of H-1-receptor antagonists

    Y Sugimoto, E Kawamoto, Z Chen, C Kamei

    IMMUNOPHARMACOLOGY   48 ( 1 )   1 - 7   2000.6

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    An animal model of chronic allergic rhinitis was developed by repeated local booster sensitization into the nasal cavity in sensitized rats. The severity of allergic rhinitis was assessed by determining the extent of two markers of nasal allergic symptoms (sneezing and nasal rubbing) after antigen challenge. The number of incidents of sneezing and nasal rubbing was markedly increased during intranasal instillation of antigen in sensitized rats. The PCA titers were also markedly elevated by intranasal sensitization. Some histamine H-1-receptor antagonists such as chlorpheniramine, ketotifen, astemizole and epinastine inhibited the increase in antigen-induced nasal symptoms in a dose-related manner. Nasal rubbing was more potently inhibited by H-1-receptor antagonists than sneezing.
    In conclusion, we developed a chronic allergic rhinitis model showing nasal symptoms in rats, and this model may be useful for evaluating the effects of drugs on allergic rhinitis. (C) 2000 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0162-3109(00)00173-9

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  • Experimental allergic conjunctivitis in guinea pigs induced by Japanese cedar pollen

    M Takada, T Yamada, H Nakahara, Y Sugimoto, K Izushi, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   23 ( 5 )   566 - 569   2000.5

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    We report a new experimental allergic conjunctivitis with Japanese cedar pollen as antigen in guinea pigs, and the immunological characteristics of this model were also elucidated. Allergic conjunctivitis was developed by immunization in guinea pigs with a mixture containing Japanese cedar pollen and killed Bordetella pertussis. When local application of Japanese cedar pollen suspension 14 d after systemic immunization was performed every 3 d, remarkable conjunctivitis was observed from 20 to 35 d. Increase in vascular permeability and decrease in histamine contents of the conjunctiva were also observed after local application of antigen. Passive cutaneous anaphylactic (PCA) reactions revealed that both IgG- and IgE-rich antibodies were produced in this model. Chlorpheniramine, ketotifen and levocabastine were effective in inhibiting cedar pollen-induced conjunctivitis. Although a high concentration was needed, tranilast and amlexanox also showed significant inhibition of conjunctivitis induced by cedar pollen.

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  • The mechanism responsible for the drowsiness caused by first generation H-1 antagonists on the EEG pattern

    Y Kaneko, K Shimada, K Saitou, Y Sugimoto, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   22 ( 3 )   163 - 168   2000.4

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    The present study was performed to clarify the mechanism responsible for the drowsiness caused by first generation H-1 antagonists according to electroencephalogram activity. All H-1 antagonists used on the present study caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra of the delta and theta bands at the frontal cortex in rats. The potency of cyproheptadine was greater than those of diphenydramine and promethazine, while that of pyrilamine was less than those of the other drugs examined. The increase in EEG power spectra in the delta band induced by H-1 antagonists was antagonized by pretreatment with both histidine and physostigime. The effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenylhydramine, promethazine and cyproheptadine. The increases in EEG power spectra induced by H-1 antagonists were neither antagonized nor potentiated by 5-hydroxytryptophan. These results clearly indicate that the increases in EEG power spectra in the delta and theta bands at the frontal cortex in rats induced by first generation H-1 antagonists are responsible for both histaminergic and cholingeric mechanisms. (C) 2000 Prous Science. All rights reserved.

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  • Effects of metabolic fragments of [Arg(8)]-vasopressin on nerve growth in cultured hippocampal neurons

    T Tarumi, Y Sugimoto, Z Chen, Q Zhao, C Kamei

    BRAIN RESEARCH BULLETIN   51 ( 5 )   407 - 411   2000.3

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    The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP(4-9) caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V-1 agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V-2 agonist [deamino-Cys(1), D-Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V-1 antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V-2 antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP(4-9) and AVP(4-8) increased filopodial length in cultured hippocampal neurons by activating V-1 receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization. (C) 2000 Elsevier Science Inc.

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  • Participation of GABAergic and histaminergic systems in inhibiting amygdaloid kindled seizures

    K Ishizawa, Z Chen, C Okuma, Y Sugimoto, Y Fujii, C Kamei

    JAPANESE JOURNAL OF PHARMACOLOGY   82 ( 1 )   48 - 53   2000.1

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    The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA.

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  • Brown-Norway系ラットを用いた潰瘍性大腸炎モデルの作製

    杉本幸雄, 亀井千晃

    Ther. Res.   21 ( Suppl. 1 )   S217-S222   2000

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  • Effect of mometasone furoate by topical application on allergic rhinitis model in rats

    Y Sugimoto, K Ishizawa, K Saitou, G Suzuki, T Tarumi, H Nakahara, Y Kirino, C Kamei

    PHARMACOLOGY   61 ( 2 )   91 - 95   2000

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    The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect. Copyright (C) 2000 S. Karger AG, Basel.

    DOI: 10.1159/000028386

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  • A new model of ulcerative colitis in Brown-Norway rats.

    21 ( Suppl. 1 )   S217-S222   2000

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  • Effects of levocabastine on lipid mediator release from guinea pig lung fragments

    Y Sugimoto, Y Iba, K Ishizawa, G Suzuki, C Kawei

    ACTA MEDICA OKAYAMA   53 ( 6 )   271 - 274   1999.12

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    The effects of levocabastine, a novel histamine H-1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C-4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E-4 or thromoboxane B-2. From these findings,it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C-4 release.

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  • Effect of propolis extract on D-galactosamine-induced hepatic injury in rats

    Y Sugimoto, T Tarumi, Y Kaneko, S Isayama, N Kawai, H Sugimoto, H Yamada, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   22 ( 11 )   1237 - 1239   1999.11

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    The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

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  • Effects of intracerebroventricular injection of alpha-fluoromethylhistidine on radial maze performance in rats

    Z Chen, Y Sugimoto, C Kamei

    PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR   64 ( 3 )   513 - 518   1999.11

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    The effects of alpha-fluoromethyl-histidine (alpha-FMH) on spatial cognition were investigated using the eight arm radial maze paradigm in rats. Intracerebroventricular (ICV) injection of alpha-FMH resulted in spatial memory deficits characterized by an increase in the number of total errors (TE) and a decrease in the number of initial correct responses (ICR). There was a strong correlation between increases in the number of TE and decreases in histamine contents of the cortex and hippocampus regions of the brain, which are known to participate in learning and memory. On the other hand, both histamine (50-100 ng, ICV) and thioperamide (10 mu g, ICV) significantly ameliorated the memory deficit induced by alpha-FMH. However, metoprine showed no significant effect on the alpha-FMH-induced memory deficit. Pyrilamine and R-(alpha)-methylhistamine enhanced the memory deficit induced by alpha-FMH, at doses that had no appreciable effect when administered alone. In contrast, no significant influence on alpha-FMH-induced memory deficit was observed with zolantidine. (C) 1999 Elsevier Science Inc.

    DOI: 10.1016/S0091-3057(99)00128-8

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  • Effects of histamine and related compounds on regional cerebral blood flow in rats

    G Suzuki, Z Chen, Sugimoto, Y, Y Fujii, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   21 ( 9 )   613 - 617   1999.11

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    The effects of histamine and related compounds on regional cerebral bloodflow (rCBF) in the hippocampus of conscious rats were studied. Intracerebroventricular injection of histamine caused a dose-dependent increase in rCBF in the hippocampus, and similar findings were observed with not only the H-1 agonist, 2-thiazolylethylamine, but also the H-2 agonist, dimaprit. Intraperitoneal injection of L-histidine also resulted in an increase in rCBF in the hippocampus, in parallel with elevation of histamine content in the brain. The increase in rCBF in the hippocampus induced by L-histidine was antagonized by both H-1 and H-2 antagonists (diphenhydramine, pyrilamine and zolantidine). In addition, when both antagonists were injected simultaneously, an additive effect was observed in antagonism of the L-histidine-induced increase in rCBF L-histidine caused no marked changes in blood pressure even at a dose of 1,500 mg/kg, which showed an increase in rCBF in the hippocampus. These results indicate that histamine elicited tm increase in rCBF via both H-1 and H-2 receptors. (C) 1999 Prous Science. All rights reserved.

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  • Slow wave sleep-inducing effects of first generation H-1-antagonists

    K Saitou, Y Kaneko, Y Sugimoto, Z Chen, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   22 ( 10 )   1079 - 1082   1999.10

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    The present study was performed to see if first-generation histamine H-1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H-1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep), The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H-1-antagonists and brotizolam. The order of potency of H-1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine, Brotizolam was more potent than these H-1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H-1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

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  • Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats

    Z Chen, Q Zhao, Y Sugimoto, Y Fujii, C Kamei

    BRAIN RESEARCH   839 ( 1 )   186 - 189   1999.8

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    The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H-1-receptors. (C) 1999 Elsevier Science B.V. All rights reserved.

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  • [Arg(8)]-Vasopressin-induced increase in intracellular Ca2+ concentration in cultured rat hippocampal neurons

    T Mihara, T Tarumi, Y Sugimoto, Z Chen, C Kamei

    BRAIN RESEARCH BULLETIN   49 ( 5 )   343 - 347   1999.7

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    Changes in intracellular Ca2+ concentration ([Ca2+](i)) induced by [Arg(8)]-vasopressin (AVP) were studied in cultured rat hippocampal neurons by fura-2 fluorometry. AVP (10-1,000 nM) caused a dose-dependent increase in [Ca2+](i). The selective V-1 vasopressin receptor agonist [Phe(2), Ile(3), Orn(8)]-vasopressin also induced a significant increase in [Ca2+](i), whereas the selective V-2 vasopressin receptor agonist [deamino Cys(1), D-Arg(8)]-vasopressin showed no effect. The AVP-induced increase in [Ca2+](i) was inhibited by the selective V-1 vasopressin receptor antagonist d(CH2)(5)[Tyr(2)(Me), Arg(8)]-vasopressin and nonpeptide V, antagonist OPC-21268. On the other hand, no antagonistic effects were observed with the V vasopressin antagonist desglycinamide-[d(CH2)(5), D-Ile(2), Ile(4), Arg(8)]-vasopressin and nonpeptide V-2 antagonist OPC-31260, The increase in [Ca2+](i) induced by AVP was abolished after removal of extracellular Ca2+. In addition, AVP-induced [Ca2+](i) elevation was not affected by treatment with verapamil, which blocked the [Ca2+](i) increase induced by an isotonic high K+-medium (50 mM), However, omega-conotoxin GVIA completely inhibited the effect of AVP, These results suggested that the AVP-induced [Ca2+](i) increase in cultured rat hippocampal neurons is due to influx of Ca2+ through V-1 VP receptors coupled with N-type calcium channels. (C) 1999 Elsevier Science Inc.

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  • Effects of Fujibitol, a remedy for nasal symptoms of immediate and delayed type allergic reactions

    M Kakimoto, N Takasugi, T Fuwa, H Saito, Y Sugimoto, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   21 ( 5 )   353 - 356   1999.6

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    The effects of Fujibitol, a remedy for the nasal symptoms of immediate and delayed type allergic reactions were studied. Fujibitol inhibited active systemic anaphylaxis in mice, heterologous passive cutaneous anaphylaxis (PCA) in rats, Masugi's nephritis in rats and delayed type hypersensitivity induced by picryl chloride in mice, but did not affect homologous PCA or immune complex-induced glomerulonephritis in rats. These results suggested that Fujibitol is effective for treatment of allergy-induced inflammation since Ige and type IV allergic reactions were inhibited. (C)1999 Prous Science. All rights reserved.

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  • Effects of anti-parkinsonian drugs on neurobehavioural changes induced by bilateral 6-hydroxydopamine lesions in rats

    T Hayakawa, Y Sugimoto, Z Chen, Y Fujii, C Kamei

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY   26 ( 5-6 )   421 - 425   1999.5

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    1. Effects of anti-Parkinsonian drugs on neurobehavioural changes induced by bilateral lesions of dopaminergic neurons were investigated in rats.
    2. Dopaminergic neurons in rats were lesioned bilaterally by injection of 6-hydroxydopamine (6-OHDA; 8 mu g) into the medial forebrain bundle at the level of the posterolateral hypothalamus. As a result, a decrease in locomotor activity and marked catalepsy and prolongation of grasping time were observed.
    3. Levodopa, talipexole, bromocriptine and theophylline dose-dependently antagonized the decrease in locomotor activity induced by bilateral 6-OHDA lesions. These drugs also showed antagonistic effects on the appearance of catalepsy and prolongation of grasping time induced by bilateral 6-OHDA lesions. In contrast, trihexyphenidyl showed no antagonizing effect on the neurobehavioural changes induced by 6-OHDA lesions at any concentration tested.
    4, Combined treatment with levodopa and talipexole antagonized the neurobehavioural changes induced by bilateral 6-OHDA lesions, whereas no marked changes were observed when either drug was administered separately, The same findings were noted with the simultaneous use of either levodopa (2 mg/kg) and theophylline (2 mg/kg) or talipexole (0.005 mg/kg) and theophylline (2 mg/kg).
    5, These results indicate that this model may be useful for estimating the effects of drugs in the treatment of Parkinson's disease.

    DOI: 10.1046/j.1440-1681.1999.03051.x

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  • 塩酸ジフェンヒドラミンによる睡眠導入作用の検討

    亀井千晃, 齊藤康一, 杉本幸雄, 陳 忠, 趙 秋蛾

    薬理と治療   27 ( 5 )   777 - 781   1999

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  • Characterization of intestinal histamine contents in Brown-Norway rats. -Influence of actively sensitization-

    20 ( Suppl. 1 )   S29-S34   1999

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  • Brown-Norway系ラットにおける消化管ヒスタミン含量の特徴−能動感作による影響−

    杉本幸雄, 亀井千晃

    セラピューティック・リサーチ   20 ( Suppl. 1 )   S29-S34   1999

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  • Studies on the sleep-inducing effect of diphenhydramine hydrochloride.

    27 ( 5 )   777 - 781   1999

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  • Strain differences in histamine release from peritoneal mast cells in rats

    Y Sugimoto, H Ohishi, T Toyota, C Kamei

    GENERAL PHARMACOLOGY   31 ( 4 )   613 - 616   1998.10

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    1. Peritoneal mast cells from Brown-Norway (BN) rats were compared with those from Wistar and Sprague-Dawley (SD) rats.
    2. Peritoneal mast cells from BN rats showed the smallest values in number, cell diameter and histamine contents compared with those from Wistar and SD rats.
    3. BN rat peritoneal mast cells were more sensitive to compound 48/80 and anti-IgE than were those from Wistar and SD rats, and they showed a higher response to A23187 than did cells from Wistar rats.
    4. The histamine release from passively sensitized peritoneal mast cells was weaker in BN rats than was that from Wistar and SD rats. (C) 1998 Elsevier Science Inc.

    DOI: 10.1016/S0306-3623(98)00063-9

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  • Effects of antiallergic drugs on histamine release from rat peritoneal mast cells induced by bradykinin

    Y Sugimoto, T Tarumi, QE Zhao, Y Fujii, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   20 ( 6 )   457 - 462   1998.7

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    Effects of antiallergic drugs on bradykinin-induced histamine release and intracellular Ca2+ release from peritoneal mast cells were studied ill mrs. Bradykinin caused a concentration-dependent histamine release as well as Ca2+ release from the intracellular Ca store of peritoneal mast cells. Antiallergic drugs used in tills study showed an inhibition of not only histamine release but also Ca2+ release. The Ca2+ release from the intracellular Ca store induced by bradykinin was more sensitive to antiallergic drugs than histamine release from mast cells. Mequitazine and terfenadine caused potent inhibitory effects oil both responses, whereas effects of ketotifen and cromolyn sodium were relatively weak. In conclusion, histamine release from mast cells and intracellular C2+ release induced by bradykinin were inhibited by antiallergic drugs similar to those induced by substance P and compound 48/80. (C) 1998 Prous Science. All rights reserved.

    DOI: 10.1358/mf.1998.20.6.485708

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  • Effects of histamine H-1 receptor antagonists on compound 48/80-induced scratching behavior in mice

    Y Sugimoto, K Umakoshi, N Nojiri, C Kamei

    EUROPEAN JOURNAL OF PHARMACOLOGY   351 ( 1 )   1 - 5   1998.6

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    The effects of histamine H-1 receptor antagonists on compound 48/80-induced scratching behavior were studied in mice. Classical histamine H-1 receptor antagonists such as diphenhydramine and chlorpheniramine caused a potent depressant effect on compound 48/80-induced scratching behavior. Histamine H-1 receptor antagonists having antiallergic activity (an inhibition of mast cell degranulation), such as azelastine and oxatomide and nonsedative histamine H-1 receptor antagonists such as terfenadine, epinastine and astemizole, also showed a relatively potent effect. On the other hand, the effects of tranilast and cromolyn sodium-antiallergic drugs without histamine H-1 receptor antagonistic activity-were extremely weak. Diazepam had weak or no depressant effects on compound 48/80-induced scratching behavior. These results suggest that inhibition of compound 48/80-induced scratching behavior is mainly due to histamine H-1 receptor antagonistic activity and not to the sedative action of the drugs. (C) 1998 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0014-2999(98)00288-X

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  • Characterization of ASK mice, a strain highly sensitive to anaphylactic shock

    H Ohmori, Y Okada, M Hikida, M Mori, Y Sugimoto, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   21 ( 3 )   219 - 223   1998.3

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    A mouse strain named ASK that was originally isolated from El (epilepsy) mice has been shown to be highly sensitive to anaphylactic shock. Here, we characterized the bases of the sensitivity of ASK mice in comparison with the parental strain, El. More than 90% of ASIC mice, but not El mice that had been sensitized either actively or passively, died within 1 h following an antigen challenge. The anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3-fold increase was observed in El mice. All (ElxASK) F-1 mice, either male or female, showed an ASK-like phenotype, suggesting that the impaired plasma histamine response in El mice is due to some recessive mutation(s). Consistent with the plasma histamine responses. cultured mast cells derived from EI bone marrow showed impaired potency to degranulate in response to surface IgE engagement, in contrast to ASK mast cells which undergo normal degranulation. Another characteristic feature of ASK mice is their sensitivity to histamine, since 75% of the mice were killed by the subcutaneous administration of 100-200 mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg histamine. Taken together, the major bases of the susceptibility to anaphylactic shock in ASK mice are thought to be the enhanced sensitivity to histamine and the recovered degranulation machinery in mast cells that is impaired in El mice.

    DOI: 10.1248/bpb.21.219

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  • Brown-Norway系ラットにおける消化管ヒスタミン含量の特徴

    杉本幸雄, 片山裕美子, 亀井千晃

    セラピューティック ・ リサーチ   19 ( Suppl.1 )   S170-S175   1998

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  • Role of substance P in experimental allergic conjunctivitis in guinea pigs

    M Yamaji, M Takada, R Fujiwara, H Ohishi, K Izushi, Y Sugimoto, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   19 ( 9 )   637 - 643   1997.11

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    The role of substance P in experimental allergic conjunctivitis induced by egg albumin was investigated with guinea pigs. Increase in vascular permeability of the conjunctiva induced by antigen was significantly inhibited after repealed application of capsaicin. Substance P contents in rite conjunctiva of guinea pig were decreased by typical instillation of antigen to rite eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover subconjunctival injection of substance P resulted in a close-related conjunctivitis, and vascular permeability iii the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, bur no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were nor influenced by subconjunctival injection of substance P. However, topical application of antigen and subconjunctival injection of compound 48/80 caused a significant decrease in histamine content, and content of tear was increased by both treatments. An increase in vascular permeability induced by antigen application was significantly inhibited by intravenous injection of FK-888, which is a specific and potent NK1 receptor antagonist. From these results, it is suggested that substance P is responsible for allergic conjunctivitis to some extent, and the conjunctival hyperpermeability induced by substance P occurs through NK1 receptor on the blood vessels, rather than by the direct action on the conjunctival mast cells during allergic conjunctival reactions.

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  • Effects of apafant on PAF-induced downregulation of beta-adrenoceptors in guinea pigs

    Y Sugimoto, Y Nakayama, H Kishida, T Hayakawa, R Fujiwara, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   19 ( 8 )   547 - 552   1997.10

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    We examined the effects of platelet-activating factor (PAF) on beta-adrenoceptors and the functional response to isoproterenol in guinea pig parenchymal strips. PAF caused a reduction in the relaxation of guinea pig lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol. In addition, PAF decreased the density of beta-adrenoceptors in guinea pig lung without any change in the affinity. Apafant, a potent PAF antagonist, inhibited the above changes, indicating that it inhibited the downregulation of beta-adrenoceptors. These findings suggest that apafant may be effective in nonspecific airway hyperreactivity in asthma.

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  • Effect of apafant on bronchial hyperresponsiveness and down-regulation of beta-adrenoceptors induced by endotoxin in guinea pigs

    Y Sugimoto, T Mihara, T Hayakawa, Y Nakayama, H Kishida, C Kamei

    ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH   47 ( 7 )   837 - 841   1997.7

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    Intraperitoneal injection of endotoxin resulted in bronchial hyperreactivity to histamine in guinea pigs. In addition, endotoxin (lipopolysaccharide, LPS) caused a decrease in the relaxation of the lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Apafant (GAS 105219-56-5, WEB 2086) was effective in the prevention of endotoxin-induced changes, i.e., bronchial hyperreactivity to histamine, a decrease in the relaxation of lung parenchymal strips induced by isoproterenol and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Ketotifen and ozagrel also prevented the bronchial hyperresponsiveness and endotoxin-induced deterioration of the beta-adrenergic system. No remarkable effect was observed with cromolyn sodium and salbutamol in the bronchial hyperreactivity to histamine induced by endotoxin in guinea pigs. Cromolyn sodium also caused no influence on the down-regulation of beta-adrenoceptors.

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  • Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats

    C Kamei, Z Chen, S Nakamura, Y Sugimoto

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   19 ( 4 )   253 - 259   1997.5

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    The influence of bilateral hippocampal lesions on active avoidance response was studied in rats, as well as the effect of intracerebroventricular (i.c.v.) injection of histamine on memory deficits caused by hippocampectomy. Retardation of learning acquisition was produced by lesioning of the the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured by open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior. I.c.v. injection of histamine and i.p. injection of histidine resulted in an improvement of memory deficits (not only learning acquisition but also memory retrieval) induced by hippocampal lesions in mrs. Histamine contents of the hippocampus and hypothalamus decreased after hippocampectomy, and a decrease in histamine contents of both areas was restored by histamine (i.c.v.) and histidine (i.p.) injection. In addition, a close relationship was found between decrease in response latency of avoidance response and an increase in histamine content of the hippocampus and hypothalamus after histamine injection.

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  • Effect of histamine and its related compounds on impairment of passive avoidance response lollowing hippocampal lesions in rats.

    Zhong Chen, Yukio Sugimoto, Chiaki Kamei

    J. Brain Sci.   23   225 - 240   1997

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  • Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin and its inhibition by a calcium antagonist, nicardipine

    C Kamei, Y Sugimoto, H Ohishi, Y Okumura, K Kitazumi

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   18 ( 9 )   579 - 588   1996.11

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    Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac ethyl adn aspirin DL-lysine showed a spike or spike and wave complex in EEG without showing remarkable behavioral changes when they were injected intraventricularly, although a relatively high dose was needed. Enoxacin, on the other hand, elicited potent epileptogenic activity characterized by uninterrupted high voltage spike and wave complex at doses of 50 and 100 mu g. At the same time,rats showed hyperactivity, jumping and violent convulsion. Combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.) caused potent epileptogenic activity characterized by uninterrupted burst of high voltage spike and wave complex. Behaviorally, animals showed forelimb clonus, head nodding and generalized convulsion. High voltage spike and wave complex was also observed after combined treatment with enoxacin (i. vent.) and ferubinac ethyl (i.v. or i. vent) in association with hyperactivity and jumping and violent convulsion. Nicardipine remarkably inhibited epileptic seizures induced by combined treatment with enoxacin (p.o) and ferubinac ethyl (i.v.). It is concluded that simultaneous treatment with enoxacin and ferubinac ethyl produced epileptogenic activity when injected intraventricularly, and nicardipine inhibited convulsions induced by combined use of enoxacin (p.o.) and ferubinac ethyl (i.v.).

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  • Effects of histamine and related compounds on the bovine iris dilator

    C Kamei, Y Sugimoto, Y Okumura

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   18 ( 4 )   273 - 278   1996.5

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    Effects of histamine and related compounds on the bovine iris dilator were investigated. Histamine caused a concentration-related contraction of the bovine iris dilator and IC50 was 1.57 x 10(-7) M. The potency of histamine on the bovine iris dilator was almost the same as that observed in guinea pig ileum. Histamine-induced contraction of the bovine iris dilator was antagonized by the H-1 antagonists pyrilamine, diphenhydramine and chlorpheniramine, whereas pretreatment with the H-2 antagonists cimetidine and ranitidine was not effective. In addition, histamine, and the H-1 agonist 2-methylhistamine caused a contraction of bovine iris dilator; but the H-2 agonist 4-methylhistamine was not effective. An H-3 antagonist, thioperamide, also had no contractive effects on the bovine iris dilator. The bovine iris dilator contained a considerable amount of histamine, which was not released by compound 48/80, substance P or by increasing K+ concentration in the medium. In conclusion, histamine caused a potent contraction of the bovine iris dilator via H-1 receptor, and this muscle showed a high sensitivity to histamine similar to guinea pig ileum.

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  • Mechanism of bradykinin-induced histamine release from rat peritoneal mast cells

    QE Zhao, T Mihara, Y Sugimoto, C Kamei

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   19 ( 2 )   237 - 240   1996.2

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    Bradykinin at concentrations higher than 2 mu M caused a significant histamine release from rat peritoneal mast cells when estracellular Ca2+ was removed from the medium. Under the same experimental conditions, bradykinin increased Ca2+ release from the intracellular Ca store of the rat peritoneal mast cells, and a clear relationship was observed between the magnitude of histamine release and an increase in fluorescence intensity. Addition of Ca2+ to the medium resulted in an inhibition of the response to bradykinin in a concentration-dependent manner. Almost the same results were obtained when Mg2+, Ba2+ and La3+ were added to the medium. Neither B-1 nor B-2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B-2 antagonists caused a histamine release of the same potency as bradykinin when applied alone. These results indicate that bradykinin-induced histamine release is not attributable to a bradykinin receptor.

    DOI: 10.1248/bpb.19.237

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  • 抗原抗体反応によるHistamine遊離に対するLoratadineの影響

    亀井千晃, 杉本幸雄, 山地雅子, 高田美穂

    薬理と治療   24 ( 1 )   49 - 52   1996

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  • Role of substance P in experimental conianctivitis in guinea pigs.

    13 ( 3 )   419 - 421   1996

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  • モルモットの実験的アレルギー性結膜炎に対するSubstance Pの関与

    山地雅子, 高田美穂, 出石啓治, 杉本幸雄, 亀井千晃

    あたらしい眼科   13 ( 3 )   419 - 421   1996

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  • Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice

    Z Chen, Y Sugimoto, C Kamei

    METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY   17 ( 10 )   669 - 675   1995.12

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    Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.0-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H-1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H-2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H-1-antagonists (diphenhydramine and chlorpheniramine) but also H-2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H-3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-a-methylhistamine, a selective H-3 agonist. In addition, the effect induced by thioperamide was inhibited by H-1 and H-2 antagonists, indicating that the H-3 receptor also participates in histamine-induced hypothermia.

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  • EFFECT OF (Z)-11-[3-(DIMETHYLAMINO)PROPYLIDENE]-6,11-DIHYDRODIBENZ[B,E]OXEPIN-2-ACETIC ACID HYDROCHLORIDE ON EXPERIMENTAL ALLERGIC CONJUCTIVITIS AND RHINITIS IN RATS AND GUINEA-PIGS

    C KAMEI, Y SUGIMOTO, S NAKAMURA, C ZHONG

    ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH   45-2 ( 9 )   1005 - 1008   1995.9

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    The effect of KW-4679 ((Z)-11-[3-(dimethylamino) propylidene)-6,11-dihydrodibenz [b, e] oxepin-2-acetic acid hydrochloride, CAS 140462-76-6; proposed INN: olopatadine) on experimental conjunctivitis and rhinitis was studied in comparison with that of ketotifen (CAS 34580-14-8) using guinea pigs and rats, respectively. KW-4679 was effective in inhibiting the antigen- and histamine-induced conjunctivitis by both oral and topical administrations. These effects of KW-4679 were somewhat more potent than those of ketotifen. KW-4679 as well as ketotifen was moi e effective in inhibiting the histamine-induced conjunctivitis than that seen in antigen-induced conjunctivitis when they were given topically. KW-4679 inhibited the increased dye leakage into the nasal cavity induced not only by antigen in actively sensitized rats but also by histamine perfusion in non-sensitized mts by oral and topical administrations. Similar to ketotifen, the effect of KW-4679 on histamine-induced increase in dye leakage was almost same as that induced by antigen. The potency of KW-4679 was higher than that of ketotifen in the ina eased dye leakage induced by both antigen and histamine perfusion.

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  • Effect of mometasone furoate on experimetal allergic rhinitis in rats.

    Chiaki Kamei, Yukio Sugimoto, Hiroshi Kakinoki, Takayuki Izumo, Chikako Ichiki

    Japanese Pharmacology&therapeutics   23 ( 11 )   2979 - 2982   1995

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  • THE ROLE OF IONS ON HISTAMINE-INDUCED DEPOLARIZATION IN ISOLATED GUINEA-PIG ADIPOCYTES

    C KAMEI, Y SUGIMOTO

    JAPANESE JOURNAL OF PHARMACOLOGY   66 ( 4 )   465 - 469   1994.12

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    Effects of ions on histamine (Hi)-induced depolarization were studied in guinea pig adipocytes. Depolarization induced by Hi in guinea pig adipocytes was decreased by removal of K+ from the medium or pretreatment with ouabain at concentrations that showed no significant effect themselves. The decrease in membrane potentials induced by Hi was also abolished potently by replacement of Na+ by choline or pretreatment with tetrodotoxin at a concentration that caused no significant action alone. Pretreatment with monensin at a concentration lower than that eliciting the action resulted in a potentiation of Hi-induced depolarization. The depolarization induced by Hi was not affected by the presence of Ca2+ in the medium or pretreatment of the cells by diltiazem.

    DOI: 10.1254/jjp.66.465

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  • X線造影剤の開発における安全性学的検討 -ラット大槽内用与による急性毒性と赤血球に及ぼす影響について-

    亀井千晃, 杉本幸雄, 竹内智子, 安部智之, 出雲貴幸, 安倉寿子

    基礎と臨床   28 ( 12 )   3795 - 3803   1994

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  • SEQUENTIAL-ANALYSIS OF HISTAMINE-RELEASE AND INTRACELLULAR CA-2+ RELEASE FROM MURINE MAST-CELLS

    K TASAKA, Y SUGIMOTO, M MIO

    INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY   91 ( 2 )   211 - 213   1990.2

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  • INFLUENCE OF AGING ON THE HISTAMINE-RELEASE AND MEMBRANE FLUIDITY OF RAT PERITONEAL MAST-CELLS

    M MIO, H AKAHORI, Y SUGIMOTO, M AKAGI, K TASAKA

    PHARMACOLOGY   38 ( 3 )   191 - 200   1989.3

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  • The Antihypertensive Effect of Consecutive Administration of Nisoldipine in Spontaneously Hypertensive Rats

    Kenji Tasaka, Chiaki Kamei, Tadami Hokonohara, Yukio Sugimoto

    Japanese Pharmacology & Therapeutics   17 ( 4 )   1545 - 1551   1989

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  • THE EFFECTS OF CEPHEM ANTIBIOTICS AND RELATED-COMPOUNDS ON THE ALDEHYDE DEHYDROGENASE IN RAT-LIVER MITOCHONDRIA

    C KAMEI, Y SUGIMOTO, K TASAKA

    BIOCHEMICAL PHARMACOLOGY   36 ( 12 )   1933 - 1939   1987.6

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    DOI: 10.1016/0006-2952(87)90491-6

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  • ANTIHYPERTENSIVE EFFECTS OF NISOLDIPINE AND REFERENCE DRUGS IN CERTAIN TYPES OF HYPERTENSIVE RATS

    K TASAKA, C KAMEI, H TAGAMI, T HOKONOHARA, Y SUGIMOTO

    ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH   37 ( 3 )   316 - 321   1987.3

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  • EFFECTS OF VARIOUS CEPHEM ANTIBIOTICS ON ETHANOL-METABOLISM AND THEIR STRUCTURE-ACTIVITY RELATIONS

    C KAMEI, Y SUGIMOTO, N MUROI, K TASAKA

    JOURNAL OF PHARMACY AND PHARMACOLOGY   38 ( 11 )   823 - 828   1986.11

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    Language:English   Publisher:ROYAL PHARMACEUTICAL SOC GREAT BRITAIN  

    DOI: 10.1111/j.2042-7158.1986.tb04502.x

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Presentations

  • Antiallergic effect of white rice on experimental allergic rhinitis model in mice

    Yukio Sugimoto, Atsushi Ogura, Hisanori Kobara, Yasutune Maruyama, Hideyuki Ito

    ICoFF2019  2019.12.3 

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    Event date: 2019.12.1 - 2019.12.5

    Presentation type:Poster presentation  

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  • チシャトウおよびその含有成分混合物の抗アレルギー作用に関する基礎的研究

    杉本幸雄, 武田侑子, 坪井駿尚, 藤原克成, 小椋敦司, 趙 秋娥, 我如古菜月, 伊東秀之, 辻本まどか, 佐伯綾希子, 林 泰資

    第73回日本栄養・食糧学会大会  2019.5.18 

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    Event date: 2019.5.17 - 2019.5.19

    Presentation type:Oral presentation (general)  

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  • チシャトウおよびその含有成分の抗アレルギー作用に関する基礎的研究

    杉本幸雄, 坪井駿尚, 稲垣勇翔, 武田侑子, 藤本啓太, 藤原克成, 趙 秋娥, 川脇美祐, 土海ちあき, 我如古菜月, 伊東秀之, 佐伯綾希子, 林 泰資

    第72回日本栄養・食糧学会大会  2018.5.11 

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    Event date: 2018.5.11 - 2018.5.13

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  • アレルギー性皮膚疾患モデルにおけるチシャトウ及びその含有成分の抑制効果

    日本薬学会第138年会  2018 

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  • チシャトウおよびその含有成分の抗アレルギー作用に関する研究

    日本農芸化学会2017年度大会  2017 

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  • チシャトウおよびその含有成分の抗アレルギー作用機序に関する研究

    日本薬学会第137年会  2017 

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  • カフェインの鼻炎抑制機序に関する検討

    第49回日本栄養·食糧学会 中国·四国支部大会  2016 

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  • 日韓の薬学教育システム比較に基づく双方向的学生教育支援―薬学部学生の体験的英語授業聴講―

    第1回日本薬学教育学会大会  2016 

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  • チシャトウの抗アレルギー作用に関する基礎的研究

    第70回日本栄養・食糧学会大会  2016 

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  • チシャトウの抗アレルギー作用機序に関する研究

    日本薬学会第136年会  2016 

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  • Antiallergic effect of stem lettuce on experimental allergic disease model in mice

    12th Asian Congress of Nutrition (ACN2015)  2015 

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  • アレルギー性皮膚疾患モデルマウスにおけるチシャトウの抑制効果

    日本薬学会第135年会  2015 

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  • 隔離飼育マウスのアレルギー性鼻炎症状に対するコーヒー揮発性成分の効果

    日本味と匂学会第48回大会  2014 

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  • 薬物誘発掻痒行動に対するPPARアゴニストの効果

    第61回日本アレルギー学会秋季学術大会  2011 

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  • アレルギー性鼻炎に対するステロイド点鼻薬の新規作用メカニズムの解明

    第61回日本アレルギー学会秋季学術大会  2011 

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  • ゲラニインおよびその代謝物の抗炎症作用

    日本薬学会第131年会  2011 

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  • ポリフェノール代謝産物の抗酸化作用および抗炎症作用

    第4回食品薬学シンポジウム  2011 

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  • エラジタンニン代謝産物Urolithin Aの抗炎症活性

    日本生薬学会第58回年会  2011 

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  • 新規低脂溶性RARβ選択的アゴニストの創製研究

    日本薬学会第130年会  2010 

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  • ヒスタミン誘発掻痒行動および血管透過性亢進反応に対するPPARアゴニストの効果

    第60回日本アレルギー学会秋季学術大会  2010 

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  • NO の被観血的、非侵襲的な定量法の開発とアレルギーモデルでの検証

    日本薬学会第130年会  2010 

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  • パーミッシブ機構に着目したRXR パーシャルアゴニストの挙動検証

    日本薬学会第130年会  2010 

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  • 薬物誘発鼻症状に対するステロイド点鼻薬の効果

    第60回日本アレルギー学会秋季学術大会  2010 

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  • RXR アゴニストのマウスアレルギー性鼻炎モデルに対する効果についての検討

    第60回日本アレルギー学会秋季学術大会  2010 

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  • 核内受容体 RXR アゴニストの抗アレルギー作用について

    第115回日本薬理学会近畿部会  2009 

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  • 白血病治療薬を志向した新規低脂溶性RARβ選択的アゴニストの創製研究

    第28回メディシナルケミストリーシンポジウム  2009 

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  • RXRアゴニストNEt-3IPの樹状細胞分化抑制・制御性T細胞誘導能と抗アレルギー作用

    第28回メディシナルケミストリーシンポジウム  2009 

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  • 核内受容体 RXR アゴニストのマウス鼻アレルギーモデルに対する効果について

    第116回日本薬理学会近畿部会  2009 

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  • 核内受容体 RXR およびPPARγの炎症に対する関与

    第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • 慢性関節炎リウマチに対するRXRアゴニストNEt-3IPの有用性について

    日本レチノイド研究会第20回学術集会  2009 

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  • Pioglitazoneの抗炎症作用における作用機序に関する研究

    第116回日本薬理学会近畿部会  2009 

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  • RXRアゴニストNEt-3IPの抗炎症作用に関する検討

    第59回日本アレルギー学会秋季学術大会  2009 

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  • ヒスタミン誘発掻痒行動および血管透過性亢進反応に対するPPARアゴニストの効果

    第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • ヒスタミン誘発鼻症状に対するモメタゾンの効果

    第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2009 

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  • カラゲニン浮腫試験に対するRXRアゴニストNEt-3IPの効果

    第115回日本薬理学会近畿部会  2009 

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  • RXRアゴニストNEt-3IPの抗アレルギー作用について

    日本薬学会第129年会  2009 

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  • アレルギー性鼻炎モデルに対する核内受容体 RXR アゴニストの作用

    第59回日本アレルギー学会秋季学術大会  2009 

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  • RXRα/βデュアルアゴニストNEt-3IPの開発と生理活性評価

    日本薬学会第128年会  2008 

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  • 新規シクロオキシゲナーゼ1(COX-1)阻害剤の開発とその胃潰瘍形成の有無および鎮痛効果の検証

    日本薬学会第128年会  2008 

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  • モルヒネおよびフェンタニル誘発掻痒行動に対する末梢性オピオイド拮抗薬の影響

    第113回日本薬理学会近畿部会  2008 

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  • アレルギー性鼻炎に対する5-アミノサリチル酸の効果

    日本薬学会第128年会  2008 

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  • マウスのアレルギー性結膜炎モデルに対する脂質メディエーター関連化合物の効果

    第28回日本眼薬理学会  2008 

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  • RXRα/β選択的デュアルアゴニストNEt-3IPの抗アレルギー作用について

    日本レチノイド研究会第19回学術集会  2008 

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  • アレルギー性鼻炎モデルに対するスルファサラジンおよびその関連化合物の効果

    第114回日本薬理学会近畿部会  2008 

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  • アレルギー性鼻炎モデルに対する5-アミノサリチル酸の効果

    第58回日本アレルギー学会秋季学術大会  2008 

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  • RXRα/βデュアルアゴニストNEt-3IPの抗アレルギー作用

    第27回メディシナルケミストリーシンポジウム  2008 

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  • 薬物誘発引っ掻き行動に対するRXRα/βデュアルアゴニストNEt-3IPの効果

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • 慢性アレルギー性鼻炎モデルに対する核内受容体RXRアゴニストNEt-3IPの効果

    第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2008 

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  • シクロオキシゲナーゼ1(COX-1)選択的阻害剤は胃潰瘍形成のない新しい鎮痛剤になりうる

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007 

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  • マウス鼻炎モデルにおける抗アレルギー薬の予防効果

    第80回日本薬理学会年会  2007 

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  • RXRα/βデュアルアゴニスト、NEt-3IPの抗炎症及び抗がん作用の検証

    第26回メディシナルケミストリーシンポジウム  2007 

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  • マウス鼻炎モデルに対する抗アレルギー薬の予防効果の検討

    第56回日本アレルギー学会秋季学術大会  2006 

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  • アレルギー性鼻炎モデルに対する抗アレルギー薬の予防効果の検討

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006 

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  • 慢性アレルギー性鼻炎モデルに対するヒスタミンH3受容体作用薬,Sch50971の抑制メカニズム

    第79回日本薬理学会年会  2006 

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  • アレルギー性鼻炎モデルに対するヒスタミンH3受容体作用薬の影響およびそのメカニズムの検討

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会(広島国際会議場  2006 

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  • アレルギー性鼻炎モデルに対するH3受容体作用薬の影響およびそのメカニズムの解明

    第56回日本アレルギー学会秋季学術大会  2006 

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  • H1受容体欠損マウスおよび肥満細胞欠損マウスにおけるカプサイシン誘発鼻掻き行動に対するオロパタジンの抑制作用

    第77回日本薬理学会年会  2004 

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  • レボカバスチンとペミロラストの併用による作用増強効果のメカニズム

    第7回日本ヒスタミン研究会  2003 

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  • H1 受容体欠損マウスおよび野生型マウスにおける抗原抗体反応による眼引っ掻き行動

    第76回日本薬理学会年会  2003 

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  • ヒスタミン H1 受容体欠損マウスを用いたオロパタジンの薬効評価

    第53回日本アレルギー学会総会  2003 

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  • レボカバスチンとペミロラスト併用による作用増強についての検討

    第53回日本アレルギー学会総会  2003 

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  • ヒスタミン H3 受容体アンタゴニストによる血管透過性亢進反応における肥満細胞の関与

    第52回日本アレルギー学会総会  2002 

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  • マウスの引っ掻き行動および血管透過性亢進反応におけるヒスタミン H3 受容体の関与

    第101回日本薬理学会近畿部会  2002 

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  • マウスの皮膚反応におけるヒスタミン H3 受容体の関与

    第43回岡山実験動物研究会  2002 

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  • マウスの引っ掻き行動および血管透過性亢進反応におけるヒスタミン H3 受容体の関与

    第41回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2002 

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  • ラットのアレルギー性結膜炎に対するリボスチンの効果

    第22回日本眼薬理学会  2002 

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  • ペパーミントに含まれる抗アレルギー成分の有効性

    日本薬学会第122年会  2002 

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  • Dextran sulfate sodium 誘発大腸炎の治癒過程におけるマスト細胞の関与

    第75回日本薬理学会年会  2002 

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  • ラットのアレルギー性結膜炎モデルの作製および薬効評価

    第52回日本アレルギー学会総会  2002 

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  • ラットの空間認知記憶における脳内ヒスタミン神経系の関与

    第5回日本ヒスタミン研究会  2001 

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  • SHR の海馬脳血流量に及ぼすバソプレッシンおよびその関連化合物の影響

    第40回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2001 

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  • ペパーミントに含まれる抗アレルギー成分の探索と有効性

    第51回日本アレルギー学会総会  2001 

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  • ラットの空間認知記憶におけるヒスチジン欠乏食の影響

    第74回日本薬理学会年会  2001 

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  • In vitro におけるラット好酸球に対するグルココルチコイドの抑制作用

    第74回日本薬理学会年会  2001 

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  • 加齢 SHR の海馬脳血流量に及ぼすバソプレッシンおよびその関連化合物の影響

    第99回日本薬理学会近畿部会  2001 

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  • ラットの空間認知記憶におけるヒスチジン欠乏食の影響

    第99回日本薬理学会近畿部会  2001 

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  • 末梢組織におけるヒスタミン H3 受容体の役割

    第74回日本薬理学会年会  2001 

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  • 皮膚反応におけるヒスタミン H3 受容体の関与

    第51回日本アレルギー学会総会  2001 

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  • 能動感作ヒスタミン H1 受容体欠損マウスを用いたアレルギー性鼻炎の解析

    第51回日本アレルギー学会総会  2001 

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  • 皮膚反応における H3 受容体の関与

    第39回日本薬学会中国四国支部大会  2000 

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  • H1 受容体欠損マウスを用いた抗原誘発引っ掻き行動に対する抗アレルギー薬の効果について

    第98回日本薬理学会近畿部会  2000 

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  • ペパーミント抽出物のラットアレルギー性鼻炎モデルに対する影響

    日本薬学会第120年会  2000 

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  • 生薬配合鼻疾患治療剤(フジビトール)のラットアレルギー性鼻炎モデルに対す影響

    日本薬学会第120年会  2000 

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  • ラット潰瘍性大腸炎モデルにおける肥満細胞の関与

    第20回ヒスタミンレセプター研究会  2000 

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  • ラットの空間認知における参照記憶と作業記憶に対するバソプレッシン誘導体の影響

    第97回日本薬理学会近畿部会  2000 

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  • マウス皮膚反応におけるヒスタミン H3 受容体の関与

    第73回日本薬理学会年会  2000 

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  • ラットの空間認知記憶に対するバソプレッシンおよびその誘導体の影響

    第39回日本薬学会中国四国支部大会  2000 

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  • The role of endogenous histamine in learning and memory in rats

    International Sendai Histamine Symposium  2000 

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  • Involvement of mast cells in inflammation sites of colitis induced by dextran sulfate sodium

    International Sendai Histamine Symposium  2000 

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  • アレルギー性鼻炎におけるヒスタミン H1 受容体の役割

    第50回日本アレルギー学会総会  2000 

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  • Dextran sulfate sodium 誘発潰瘍性大腸炎モデルにおけるマスト細胞の関与

    第96回日本薬理学会近畿部会  1999 

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  • H1-antagonist により生ずるけいれん誘発作用について

    第38回日本薬学会中国四国支部大会  1999 

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  • Effect of peppermint extract on experimental allergic rhinitis in rats

    2nd International Conference on Food Factor  1999 

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  • ペパーミント抽出物のラット抗原誘発鼻アレルギーモデルに対する効果

    第49回日本アレルギー学会総会  1999 

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  • デキストラン硫酸誘発潰瘍性大腸炎モデルにおけるマスト細胞の関与

    第49回日本アレルギー学会総会  1999 

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  • マウスのアレルギー性鼻炎モデルの作製とその応用

    第38回日本薬学会中国四国支部大会  1999 

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  • Effect of propolis extract on D-galactosamine-induced hepatic injury in rats

    XXXVIth Apimondia International Apicultural Congress  1999 

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  • Brown-Norway 系ラットを用いた潰瘍性大腸炎モデルの作製

    第19回ヒスタミンレセプター研究会  1999 

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  • ヒスタミン誘発引っ掻き行動におけるヒスタミン H1 および H2 受容体の関与について

    第49回日本アレルギー学会総会  1999 

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  • ラットの空間認知記憶における脳内ヒスタミンの関与

    第29回日本精神神経薬理学会年会  1999 

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  • ヒスタミン H1 受容体欠損マウスの皮膚反応における特徴

    第72回日本薬理学会年会  1999 

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  • ラットの8方向放射状迷路課題におけるヒスチジン欠乏食の影響

    第95回日本薬理学会近畿部会  1999 

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  • ヒスタミン H1 受容体欠損マウスを用いたアレルギー性鼻炎の解析

    日本薬学会第119年会  1999 

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