Hyperesthesia via the alteration of thermo-sensitive TRP channels in animal model of irritable bowel syndrome

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Josai International University
• Principal Investigator: HORIE Syunji Josai International University, 薬学部, 教授 (50209285)
• Project Period (FY): 2007 – 2008
• Keywords: TRPV1 / カプサイシン / TRPA1 / アリルイソチオシアネート / 下部消化管 / 内臓知覚神経 / 免疫組織化学 / ストレス

Research Abstract

精神的ストレスが積み重なると、消化管に大きな影響を与え、便通異常と痛みを伴う過敏性腸症候群というやっかいな病気に進展する。この原因を解明するために、過敏性腸症候群モデル動物を用いた研究を行った。結果として、ストレスにより消化管に知覚過敏が引き起こされており、これにはカプサイシン受容体TRPV1(43℃の熱で活性化するセンサー)の反応性が大きくなっていることが判明した。したがって、このカプサイシン受容体は新しい医薬品のターゲットになると考えている。

Research Products

• [Journal Article] Localization of TRPV1 and contractile effect of capsaicin in mouse large intestine: high abundance and sensitivity in rectum and distal colon. (2009)
  • Author(s): Matsumoto, K., Kurosawa, E., Terui, H., Hosoya, T., Tashima, K., Murayama, T., Priestley, J.V., Horie, S.
  • Journal Title: Am. J. Physiol. Gastrointest. Liver Physiol. (in press)
  • Peer Reviewed
• [Journal Article] Nicotine-induced neurogenic relaxation in the mouse colon; changes with dextran sodium sulfate-induced colitis. (2009)
  • Author(s): Murakami I., Hamada Y., Yamane S., Fujino H., Horie S., Murayama T.
  • Journal Title: J. Pharmacol. Sci. 109(1) Pages: 128-138
  • Peer Reviewed
• [Journal Article] Validation of 13C-acetic acid breath test by measuring effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice. (2008)
  • Author(s): Matsumoto, K., Kimura, H., Tashima, K., Uchida, M., Horie, S.
  • Journal Title: Biol. Pharm. Bull. 31(10) Pages: 1917-1922
  • Peer Reviewed
• [Journal Article] The Chemical Constituents of Aristolochia constricta: Antispasmodic effects of its constituents in guinea-pig ileum and isolation of a diterpeno-lignan hybrid. (2008)
  • Author(s): Zhang, G., Shimokawa, S., Mochizuki, M., Kumamoto, T., Nakanishi, W., Watanabe, T., Ishikawa, T., Matsumoto, K., Tashima, K., Horie, S., Higuchi, Y., Dominguez, O.P.
  • Journal Title: J. Natural Products 71 Pages: 1167-1172
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of transient receptor potential vanilloid subtype 1 in the trachea of ovalbumin-sensitized guinea pigs. (2008)
  • Author(s): Watanabe, N., Horie, S., Spina, D., Michael, G.J., Page, C.P., Priestley, J.V.
  • Journal Title: International Archives of Allergy and Immunology 146(1) Pages: 28-32
  • Peer Reviewed
• [Journal Article] MGM-9 [(E)-methyl 2-(3-ethyl-7a,12a-(epoxyethanoxy)-9-fluoro-1,2,3,4,6,7,12,12b-octahydro-8-methoxyindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate], a derivative of the indole alkaloid mitragynine: a novel dual-acting μ- and κ-opioid agonist with potent antinociceptive and weak rewarding effects in mice. (2008)
  • Author(s): Matsumoto, K., Takayama, H., Narita, M., Nakamura, A., Suzuki, M., Suzuki, T., Murayama, T., Wongseripipatana, S., Misawa, K., Kitajima, M., Tashima, K., Horie, S.
  • Journal Title: Neuropharmacology 55(2) Pages: 154-165
  • Peer Reviewed
• [Journal Article] トウガラシの辛味は胃でも味わう:カプサイシンのバニロイド受容体を介した胃機能への薬理作用 (2008)
  • Author(s): 堀江俊治
  • Journal Title: Food and Food Ingredients Journal of Japan 213(7) Pages: 660-665
  • Peer Reviewed
• [Journal Article] 温度と辛味を感じる受容体:消化管にとってよい受容体か?悪い受容体か? (2008)
  • Author(s): 堀江俊治、田嶋公人、松本健次郎
  • Journal Title: I. Research 16(5) Pages: 403-410
  • Peer Reviewed
• [Journal Article] Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine. Eur. (2007)
  • Author(s): Penuelas, A, Tashima, K., Tsuchiya, S., Matsumoto, K., Nakamura, T., Horie, S., Yano, S.
  • Journal Title: J. Pharmacol. 576(1-3) Pages: 143-50
  • Peer Reviewed
• [Journal Article] Effect of capsaicin via TRPV1 in isolated mouse lower gastrointestinal tract and the influence of neonatal stress. (2007)
  • Author(s): Horie, S., Matsumoto, K., Tashima, K.
  • Journal Title: Autonomic Neuroscience 135(1-2) Pages: 96-97
  • Peer Reviewed
• [Journal Article] Quercetin-induced PC12 cell death accompanied by caspase-mediated DNA fragmentation. (2007)
  • Author(s): Sasaki, M., Nakamura, H., Tsuchiya, S., Horie, S., Kashiwayanagi, M., Saito, T., Murayama, T.
  • Journal Title: Biol. Pharm. Bull. 30(4) Pages: 682-686
  • Peer Reviewed
• [Presentation] ラット胃におけるバニロイド受容体TRPV1神経の分布:脳腸ペプチド カルシトニン遺伝子関連ペプチドおよびサブスタンスPとの共存 (2009)
  • Author(s): 堀江俊治、松本健次郎、田嶋公人
  • Organizer: ワークショップ。第5回消化管学会総会
  • Place of Presentation: 東京
  • Year and Date: 20090212-13
• [Presentation] マウス摘出下部消化管におけるバニロイド受容体TRPV1の局在とカプサイシン誘起平滑筋収縮作用機序の解明 (2008)
  • Author(s): 松本健次郎、田嶋公人、堀江俊治
  • Organizer: 生体機能と創薬シンポジウム2008
  • Place of Presentation: 東京
  • Year and Date: 20080905-06
• [Presentation] Differences in localization of TRPV1 channels and contractile effect of capsaicin in mouse isolated lower gastrointestinal tract: higher abundance and sensitivity of TRPV1 channels in rectum and distal colon than in transverse and proximal colon. (2008)
  • Author(s): Kenjiro Matsumoto, Kimihito Tashima, Syunji Horie
  • Organizer: Digestive Disease Week and the 109th Annual Meeting of the American Gastroenterological Association Institute
  • Place of Presentation: Washington, D.C, USA
  • Year and Date: 20080517-22
• [Presentation] トウガラシの辛みの薬効に科学的エビデンス:胃におけるバニロイド受容体TRPV1発現神経の分布と機能 (2008)
  • Author(s): 堀江俊治
  • Organizer: 第7回神経消化器病学会(招聘講演)
  • Place of Presentation: 東京
  • Year and Date: 2008-09-30
• [Presentation] ラット培養胃粘膜細胞におけるタイトジャンクションバリアに対する温度感受性チャネルTRPV1、TRPA1作動薬の作用 (2008)
  • Author(s): 田嶋公人、佐藤翔吾、吉田実世、松本健次郎、村山俊彦、堀江俊治
  • Organizer: シンポジウム。第26回Cytoprotection研究会
  • Place of Presentation: 京都
  • Year and Date: 2008-03-14
• [Presentation] マウス直腸、遠位、横行、近位結腸におけるバニロイド受容体TRPV1の局在とカプサイシン誘起平滑筋収縮の相関 (2008)
  • Author(s): 松本健次郎、田嶋公人、堀江俊治
  • Organizer: 第26回Cytoprotection研究会
  • Place of Presentation: 京都
  • Year and Date: 2008-03-14
• [Presentation] Effect of capsaicin via TRPV1 in isolated mouse lower gastrointestinal tract and the influence of neonatal stress. (2007)
  • Author(s): Syunji Horie, Kenjiro Matsumoto, Kimihito Tashima
  • Organizer: International Society for Autonomic Neuroscience (ISAN) 2007
  • Place of Presentation: Kyoto
  • Year and Date: 20071005-08
• [Presentation] ラット胃粘膜初代培養細胞のタイトジャンクションバリアに対する温度感受性TRPV1, TRPM8, およびTRPA1チャネル作動薬の作用 (2007)
  • Author(s): 佐藤翔吾、田嶋公人、松本健次郎、土屋静子、矢野眞吾、村山俊彦、堀江俊治
  • Organizer: 第35回日本潰瘍学会
  • Place of Presentation: 鳥取
  • Year and Date: 20070921-22
• [Presentation] マウス摘出下部消化管標本におけるワサビ成分アリルイソチオシアネートの平滑筋収縮作用:低温感受性チャネルTRPA1の関与 (2007)
  • Author(s): 堀江俊治、Angelica Penuelas、土屋静子、中村智徳、矢野眞吾、松本健次郎、田嶋公人
  • Organizer: 第24回和漢医薬学会大会
  • Place of Presentation: 富山
  • Year and Date: 20070908-09
• [Presentation] Cold receptor TRPA1 mediate the smooth muscle contraction in isolated mouse lower intestinal tract. (2007)
  • Author(s): Kimihito Tashima, Penuelas Angelica, Shizuko Tsuchiya, Kenjiro Matsumoto, Tomonori Nakamura, Shingo Yano, Syunji Horie
  • Organizer: Digestive Disease Week
  • Place of Presentation: Washington, DC
  • Year and Date: 20070519-24
• [Presentation] 消化器疾患とバニロイドレセプター 辛味は消化器でも味わう:バニロイドレセプターTRPV1による消化管機能調節 (2007)
  • Author(s): 堀江俊治
  • Organizer: ランチョンセミナー。Japan Digestive Disease Week 2007
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-20