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Role of thermo-sensitive TRP channels in stress-induced visceral hyperesthesia: analyses of samples from disease model animals and patients

Research Project

Project/Area Number 24590118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionJosai International University

Principal Investigator

HORIE SYUNJI  城西国際大学, 薬学部, 教授 (50209285)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsTRPチャネル / カプサイシン / 痛覚過敏 / 知覚過敏 / 微小炎症 / ストレス / 過敏性腸症候群 / 機能性ディスペプシア / 潰瘍性大腸炎 / 食後不定愁訴症候群 / 病態モデル / TRPV1 / TRPA1 / 求心性一次知覚神経 / 知覚過敏性 / TRPM2 / 免疫組織化学 / クローン病 / 遠位結腸 / 温度感受性TRPチャネル / 機能性胃腸症 / 炎症性腸疾患 / ヒト組織標本
Outline of Final Research Achievements

Psychological stress induces impairment of gastrointestinal tracts, leading to functional gastrointestinal diseases (irritable bowel syndrome, functional dyspepsia) accompanied by abdominal pain. The present study was designed with those disease model animals in order to elucidate the causes of functional gastrointestinal diseases. As an important result, the stress induces the increased number of thermosensitive TRP channel-expressing nerve fibers, resulting in the hypersensitivity of visceral pain. Therefore, the inhibition of the abnormality of TRP channels-expressing nerves in gut will make a contribution to the treatment of functional gastrointestinal diseases.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (46 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (27 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 27 results,  Acknowledgement Compliant: 10 results,  Open Access: 8 results) Presentation (16 results) (of which Invited: 6 results) Book (3 results)

  • [Journal Article] Serotonin/5-hydroxytryptamine-3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis2016

    • Author(s)
      Utsumi D, Matsumoto K, Amagase K, Horie S, Kato S.
    • Journal Title

      Br. J. Pharmacol.,

      Volume: 173 Issue: 11 Pages: 1835-1849

    • DOI

      10.1111/bph.13482

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Differences in the morphine-induced inhibition of small and large intestinal transit: Involvement of central and peripheral µ-opioid receptors in mice2016

    • Author(s)
      Matsumoto K, Umemoto H, Mori T, Akatsu R, Saito S, Tashima K, Shibasaki M, Kato S, Suzuki T, Horie S
    • Journal Title

      Eur J Pharmacol.

      Volume: 771 Pages: 220-228

    • DOI

      10.1016/j.ejphar.2015.12.033

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] L-cysteine/d,L-homocysteine-regulated ileum motility via system L and B°,+ transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments.2015

    • Author(s)
      Yamane S, Nomura R, Yanagihara M, Nakamura H, Fujino H, Matsumoto K, Horie S, Murayama T.
    • Journal Title

      Eur J Pharmacol.

      Volume: 764 Pages: 471-479

    • DOI

      10.1016/j.ejphar.2015.07.042

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 温度感受性TRPチャネルアンタゴニスト活性を有するVoacangine型アルカロイドの探索・合成と構造活性相関研究2015

    • Author(s)
      北島満里子、寺田祐子、渡辺達夫、堀江俊治、高山廣光
    • Journal Title

      Med Chem News

      Volume: 25 Pages: 132-137

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Voacanga africana由来アルカロイドvoacangineの温度感受性TRPチャネルに対する活性・阻害作用2015

    • Author(s)
      寺田祐子、堀江俊治、北島満里子、高山廣光、渡辺達夫
    • Journal Title

      食品加工技術

      Volume: 35 Pages: 49-60

    • NAID

      40020560893

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TRPチャネルと内臓痛2015

    • Author(s)
      松本健次郎、加藤伸一、堀江俊治
    • Journal Title

      日本薬理学雑誌

      Volume: 146 Pages: 233-235

    • NAID

      130005129743

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 漢方薬特有の臨床適用を薬理学的に翻訳する2015

    • Author(s)
      堀江俊治
    • Journal Title

      漢方の臨床

      Volume: 62 Pages: 975-976

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages in postoperative ileus.2015

    • Author(s)
      Maehara T; Matsumoto K; Horiguchi K; Kondo M; Iino S; Horie S; Murata T; Tsubone H; Shimada S; Ozaki H; Hori M.
    • Journal Title

      Br J Pharmacol

      Volume: 172(4) Issue: 4 Pages: 1136-1147

    • DOI

      10.1111/bph.13006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Indole Alkaloid Structural Units Important for Stimulus-Selective TRPM8 Inhibition: SAR Study of Naturally Occurring Iboga Derivatives2014

    • Author(s)
      Yuko Terada, Mariko Kitajima, Fuyumi Taguchi, Hiromitsu Takayama, Syunji Horie, and Tatsuo Watanabe
    • Journal Title

      Journal of Natural Products

      Volume: 77 Issue: 8 Pages: 1831-1838

    • DOI

      10.1021/np500235b

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus.2014

    • Author(s)
      Matsumoto K, Hosoya T, Ishikawa E, Tashima K, Amagase K, Kato S, Murayama T, Horie S.
    • Journal Title

      Histochem Cell Biol

      Volume: 142(6) Issue: 6 Pages: 635-644

    • DOI

      10.1007/s00418-014-1246-6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circular muscle contraction in the mice rectum plays a key role in morphine-induced constipation.2014

    • Author(s)
      Ono H, Nakamura A, Matsumoto K, Horie S, Sakaguchi G, Kanemasa T.
    • Journal Title

      Neurogastroenterol Motil.

      Volume: 25(10) Issue: 10 Pages: 1396-1407

    • DOI

      10.1111/nmo.12387

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil recruitment is critical for 5-fluorouracil-induced diarrhea and the decrease in aquaporins in the colon2014

    • Author(s)
      Sakai H, Sagara A, Matsumoto K, Jo A, Hirosaki A, Takase K, Sugiyama R, Sato K, Ikegami D, Horie S, Matoba M, Narita M.
    • Journal Title

      Pharmacol. Res.

      Volume: 87 Pages: 71-79

    • DOI

      10.1016/j.phrs.2014.05.012

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM8 has a key role in experimental colitis-induced visceral hyperalgesia in mice2014

    • Author(s)
      Hosoya T, Matsumoto K, Tashima K, Nakamura H, Fujino H, Murayama T, Horie S
    • Journal Title

      Neurogastroenterol Motil

      Volume: 印刷中 Issue: 8 Pages: 1112-1121

    • DOI

      10.1111/nmo.12368

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation and Inhibition of Thermosensitive TRP Channels by Voacangine, an Alkaloid Present in Voacanga africana, an African Tree2014

    • Author(s)
      Yuko Terada, Syunji Horie, Hiromitsu Takayama, Kunitoshi Uchida, Makoto, Tominaga, and Tatsuo Watanabe
    • Journal Title

      Journal of Natural Products

      Volume: 77 Issue: 2 Pages: 285-297

    • DOI

      10.1021/np400885u

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice.2014

    • Author(s)
      Matsumoto K, Narita M, Muramatsu N, Nakayama T, Misawa K, Kitajima M, Tashima K, Devi LA, Suzuki T, Takayama H, Horie S.
    • Journal Title

      J Pharmacol Exp Ther.

      Volume: 348 Issue: 3 Pages: 383-392

    • DOI

      10.1124/jpet.113.208108

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms that underlie μ-opioid receptor agonist-induced constipation: differential involvement of μ-opioid receptor sites and responsible regions.2014

    • Author(s)
      Mori T, Shibasaki Y, Matsumoto K, Shibasaki M, Hasegawa M, Wang E, Masukawa D, Yoshizawa K, Horie S, Suzuki T.
    • Journal Title

      J Pharmacol Exp Ther.

      Volume: 347 Issue: 1 Pages: 91-99

    • DOI

      10.1124/jpet.113.204313

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bee venom phospholipase A2-induced phasic contractions in mouse rectum: Independent roles of eicosanoid and gap junction proteins and their loss in experimental colitis2013

    • Author(s)
      Nomura R, Yanagihara M, Sato H, Matsumoto K, Tashima K, Horie S, Chen S, Fujino H, Ueno K, Murayama T
    • Journal Title

      Eur J Pharmacol

      Volume: 718 Issue: 1-3 Pages: 314-322

    • DOI

      10.1016/j.ejphar.2013.08.015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuronal Nitric Oxide Synthase-Derived Nitric Oxide Is Involved in Gastric Mucosal Hyperemic Response to Capsaicin in Rats2013

    • Author(s)
      Raimura M, Tashima K, Matsumoto K, Tobe S, Chino A, Namiki T, Terasawa K, Horie
    • Journal Title

      Pharmacology

      Volume: 92 Issue: 1-2 Pages: 60-70

    • DOI

      10.1159/000351853

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of 5-HT3 and NK 1 Receptors in 5-Fluorouracil-Induced Mucositis in Mouse Jejunum2013

    • Author(s)
      Matsumoto K
    • Journal Title

      Dig Dis Sci.

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 5-Fluorouracil induces diarrhea with changes in the expression of inflammatory cytokines and aquaporins in mouse intestines.2013

    • Author(s)
      Sakai H.
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 1 Pages: e54788-e54788

    • DOI

      10.1371/journal.pone.0054788

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serotonin 5-HT(3) receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in mice intestinal crypt cells2013

    • Author(s)
      Yasuda M
    • Journal Title

      Br J Pharmacol.

      Volume: 168 Issue: 6 Pages: 1388-1400

    • DOI

      10.1111/bph.12019

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dietary agonists of TRPV1 inhibit gastric acid secretion in mice2012

    • Author(s)
      Okumi H
    • Journal Title

      Planta Med.

      Volume: 78 Pages: 1801-1806

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dual role of serotonin in the pathogenesis of indomethacin-induced small intestinal ulceration: Pro-ulcerogenic action via 5-HT3 receptors and anti-ulcerogenic action via 5-HT4 receptors2012

    • Author(s)
      Kato S
    • Journal Title

      Pharmacol Res.

      Volume: 66 Pages: 226-234

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice2012

    • Author(s)
      Matsumoto K
    • Journal Title

      Laboratory Investigation

      Volume: 92 Pages: 769-782

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decrease of guanylyl cyclase β1 subunit and nitric oxide (NO)-induced relaxation in mouse rectum with colitis and its reproduction on long-term NO treatment2012

    • Author(s)
      Hamada Y
    • Journal Title

      Naunyn-Schmiedeberg Arch. Pharmacol.

      Volume: 385 Pages: 81-94

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Subdiaphragmatic vagotomy induces a functional change in visceral Aδ primary afferent fibers in rats2012

    • Author(s)
      Furuta S
    • Journal Title

      Synapse

      Volume: 66 Pages: 369-371

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dysfunction of neurogenic VIP-mediated relaxation in mouse distal colon with dextran sulfate sodium-induced colitis2012

    • Author(s)
      Kato E
    • Journal Title

      Pharmacological Research

      Volume: 65 Pages: 204-212

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 大建中湯の胃機能への作用を解析するために胃運動減弱モデル動物を開発するー弱い薬理作用を検出するためのひと工夫ー2015

    • Author(s)
      押 範之、田嶋公人、橋本和樹、今井拓、松本健次郎、堀江俊治
    • Organizer
      第18回天然薬物研究方法論アカデミー・大子シンポジウム
    • Place of Presentation
      茨城県大子町
    • Year and Date
      2015-08-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] 覚醒下マウスにおける大建中湯の胃酸分泌抑制作用:カプサイシン受容体TRPV12015

    • Author(s)
      堀江俊治、松本健次郎、田嶋公人
    • Organizer
      第43回日本潰瘍学会
    • Place of Presentation
      沖縄科学技術大学院大学
    • Year and Date
      2015-06-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] 大建中湯の消化管機能亢進作用とTRPチャネル2015

    • Author(s)
      堀江俊治
    • Organizer
      第16回千葉消化管運動機能研究会
    • Place of Presentation
      千葉市
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Experimental colitis alters expression of serotonin receptors and transient receptor potential vanilloid type 1 (TRPV1) channels leading to visceral hypersensitivity in mice2014

    • Author(s)
      Syunji Horie , Kimihito Tashima, Kenjiro Matsumoto. .
    • Organizer
      17th World Congress of Basic & Clinical Pharmacology
    • Place of Presentation
      Cape Town, South Africa
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 漢方薬とTRPチャネル:大建中湯の薬理作用メカニズム2014

    • Author(s)
      堀江俊治
    • Organizer
      第15回千葉消化管運動機能研究会
    • Place of Presentation
      千葉市
    • Year and Date
      2014-06-26
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 胃粘膜上皮バリア機能調節における温度感受性TRP チャネルの役割2014

    • Author(s)
      堀江俊治
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本 鶴屋百貨店
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 3種類の内臓痛覚過敏モデルラットにおける桂枝可芍薬湯の作用2013

    • Author(s)
      松本健次郎、山村朋子、鈴木梨香子、田嶋公人、堀江俊治
    • Organizer
      第86回日本薬理学会年会 (福岡, 2013.3.21-23
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] 5-Fluorouracil induces diarrhea, nausea, and vomiting with alteration of aquaporins, serotonin, and neurokinin receptors in mouse intestine2013

    • Author(s)
      Kenjiro Matsumoto, Jo Odagiri, Kimihito Tashima, Syunji Horie
    • Organizer
      Digestive Disease Week 2013
    • Place of Presentation
      Orland, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] ラット腸管神経系、脊髄後根神経節におけるTRPM2チャネルの局在に関する免疫組織化学的検討2013

    • Author(s)
      松本健次郎, 渡辺智章, 五十幡陽, 高木加奈子, 田嶋公人, 堀江俊治
    • Organizer
      TRP研究会2013
    • Place of Presentation
      岡崎 生理学研究所
    • Related Report
      2013 Research-status Report
  • [Presentation] 基礎研究によって天然薬物由来成分に薬理作用があると言うためには? 古典薬理学的および化学的アプローチ2013

    • Author(s)
      堀江俊治
    • Organizer
      天然薬物研究方法論アカデミー第16回シンポジウム
    • Place of Presentation
      岐阜グランドホテル
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] TRPM2チャネルのラット腸管神経系、脊髄後根神経節における局在と内臓痛への関与2013

    • Author(s)
      松本健次郎, 渡辺智章, 五十幡陽, 高木加奈子, 田嶋公人, 堀江俊治
    • Organizer
      第15回日本神経消化器病学会
    • Place of Presentation
      島根 ビッグハート出雲
    • Related Report
      2013 Research-status Report
  • [Presentation] ワサビ辛味成分アリルイソチオシアネートは胃運動を減弱させる:胃運動低下病態モデルマウスの作製2013

    • Author(s)
      田嶋公人、松本健次郎、堀江俊治
    • Organizer
      第41回日本潰瘍学会
    • Place of Presentation
      ホテル阪急エキスポパーク
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス下部消化管摘出標本におけるアリルイソチオシアネートのワサビ受容体TRPA1を介する平滑筋収縮作用―セロトニン5-HT3および5-HT4受容体の関与―2013

    • Author(s)
      田嶋公人、松本健次郎、堀江俊治
    • Organizer
      第41回日本潰瘍学会
    • Place of Presentation
      ホテル阪急エキスポパーク
    • Related Report
      2013 Research-status Report
  • [Presentation] ワサビ辛味成分アリルイソチオシアネートによるラット胃粘膜炎症の惹起-機能性ディスペプシア病態モデル動物の開発に向けて-2013

    • Author(s)
      12. 田嶋公人、高野翔太、竹内徹也、大曽根健矢、松本健次郎、堀江俊治
    • Organizer
      第7回機能性ディスペプシア研究会
    • Place of Presentation
      島根 ビッグハート出雲
    • Related Report
      2013 Research-status Report
  • [Presentation] 漢方薬とTRPチャネル:大建中湯の薬理作用メカニズム

    • Author(s)
      堀江俊治
    • Organizer
      第15回千葉消化管運動機能研究会
    • Place of Presentation
      三井ガーデンホテル千葉
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] アリルイソチオシアネートによるラット胃粘膜炎症の惹起-TRPA1チャネルの関与-

    • Author(s)
      高野翔太、田嶋公人、竹内徹也、大曽根健矢、松本健次郎、堀江俊治
    • Organizer
      第128回日本薬理学会関東部会
    • Place of Presentation
      早稲田大学先進理工学部
    • Related Report
      2013 Research-status Report
  • [Book] Capsaicin - Sensitive Neural Afferentation and the Gastrointestinal Tract: from Bench to Bedside2014

    • Author(s)
      Tashima, K., Kabashima, M., Matsumoto, K., Yano, S., Hagen S.J., Horie, S.
    • Total Pages
      364
    • Publisher
      InTech, Rejeka, Croatia
    • Related Report
      2014 Research-status Report
  • [Book] Capsaicin - Sensitive Neural Afferentation and the Gastrointestinal Tract: from Bench to Bedside2014

    • Author(s)
      Horie, S., Raimura, M., Matsumoto, K., Namiki, T., Terasawa, K., Priestley, J.V., Tashima, K
    • Total Pages
      364
    • Publisher
      InTech, Rejeka, Croatia
    • Related Report
      2014 Research-status Report
  • [Book] 機能性ディスペプシア 日本人に適した診療を求めて2014

    • Author(s)
      堀江俊治、松本健次郎、田嶋公人
    • Total Pages
      158
    • Publisher
      フジメディカル出版
    • Related Report
      2014 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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