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2010 Fiscal Year Final Research Report

Local regulatory mechanisms of gastroduodenal bicarbonate secretion :

Research Project

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Project/Area Number 20590264
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

TAKEUCH Koji  Kyoto Pharmaceutical University, 薬学部, 教授 (00150798)

Co-Investigator(Renkei-kenkyūsha) KURIHARA Eitaro  京都薬科大学, 薬学部, 大学院生
SASAKI Yoko  京都薬科大学, 薬学部, 大学院生
KITA Kazutomo  京都薬科大学, 薬学部, 大学院生
ISE Fumitaka  京都薬科大学, 薬学部, 大学院生
OHASHI Yumi  京都薬科大学, 薬学部, 大学院生
TAKASUKA Hironori  京都薬科大学, 薬学部, 大学院生
TAKAHASHI Kento  京都薬科大学, 薬学部, 大学院生
KOYAMA Masafumi  京都薬科大学, 薬学部, 大学院生
Project Period (FY) 2008 – 2010
Keywords十二指腸アルカリ分泌 / ガス状メディエーター / 硫化水素(H_2S) / 一酸化炭素(CO) / コリン作動薬(カルバコール) / ムスカリン受容体サブタイプ / M受容体ノックアウトマウト / D細胞 / ソマトスタチン
Research Abstract

We demonstrated in the present study that 1) endogenous PGs and gas mediators such as NO, H_2S and CO, are involved in the local regulatory mechanism of the acid-induced duodenal HCO_3^- secretion, 2) NO and CO stimulate HCO_3^- secretion at least partly by increasing PG production, 3) the stimulatory action of H_2S is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurons, 4) PGE_2 stimulates HCO_3^- secretion via activation of EP3/EP4 receptors, and 5) both PDE1 and PDE3 are involved in the regulation of duodenal HCO_3^- secretion. In addition, we also found, using muscarinic (M) receptor knockout mice, that 6) the cholinergic stimulation of duodenal HCO_3^- secretion is mainly mediated by the activation of M1 and M3 receptors and modified by M4 receptors and that 7) the activation of M4 receptors inhibits the release of somatostatin from D cells and results in enhancement of the HCO_3^- response by removing the negative effect of somatostatin.

  • Research Products

    (25 results)

All 2011 2010 2009

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (15 results) Book (3 results)

  • [Journal Article] Carbon monoxide involvedin modulating HCO_3^- secretion in rat duodenums.2011

    • Author(s)
      Takasuka H, Hayashi S, Koyama M, Yasuda M, Aihara E, Amagase K. Takeuchi K
    • Journal Title

      J Pharmacol Exp Ther 337(in press)

      Pages: 293-300

    • Peer Reviewed
  • [Journal Article] Regulatory mechanism of duodenal bicarbonate secretion : Roles of endogenous prostaglandins and nitric oxide.2011

    • Author(s)
      Takeuchi K, Kita K, Hayashi S, Aihara E
    • Journal Title

      Pharmacology & Therapeutics 130

      Pages: 59-70

    • Peer Reviewed
  • [Journal Article] Stimulation of duodenal HCO_3^- secretion by hydrogen sulfide in rats : Relation to prostaglandins, nitric oxide and sensory neuron.2011

    • Author(s)
      Ise F, Takasuka H, Hayashi S, Takahashi K, Koyama M, Aihara E, Takeuchi K
    • Journal Title

      Acta Physiologica 201

      Pages: 117-126

    • Peer Reviewed
  • [Journal Article] Prostaglandin EP receptor subtypes involved in regulating HCO_3^- secretion from gastroduodenal mucosa.2010

    • Author(s)
      小山真史, 林周作, 粟飯原永太郎
    • Journal Title

      Current Pharm Design 16

      Pages: 1241-1251

    • Peer Reviewed
  • [Journal Article] 十二指腸アルカリ分泌におけるCOの影響2010

    • Author(s)
      高須賀洋徳、小山真史、林周作、粟飯原永太郎、竹内孝治
    • Journal Title

      Ulcer Research 37

      Pages: 144-148

    • Peer Reviewed
  • [Journal Article] 十二指腸重炭酸イオン分泌におけるブラジキニンの影響2009

    • Author(s)
      大橋由美、高須賀洋徳、高橋健人、粟飯原永太郎、竹内孝治
    • Journal Title

      Ulcer Research 36

      Pages: 207-210

    • Peer Reviewed
  • [Journal Article] Phosphodiesterase isozymes involved in regulating acid secretion in the isolated mouse stomach.2009

    • Author(s)
      Okuda S, Honda M, Ito Y, Aihara E, Kato S, Mitsufuji S, Yoshikawa T., Takeuchi K
    • Journal Title

      J Physiol Pharmacol 60

      Pages: 183-190

    • Peer Reviewed
  • [Presentation] 胃酸分泌におけるカルシウム感知受容体の関与2010

    • Author(s)
      小山真史、加藤伸一、竹内孝治
    • Organizer
      第38回日本潰瘍学会
    • Place of Presentation
      リーガロイヤルホテル大阪
    • Year and Date
      2010-11-19
  • [Presentation] マウス胃酸分泌におけるカルシウム感知受容体(CaSR)の役割2010

    • Author(s)
      土岸広治、小山真史、林周作、栗飯原永太郎、加藤伸一、竹内孝治
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2010
    • Place of Presentation
      京都大学
    • Year and Date
      2010-09-11
  • [Presentation] Muscarinic acetylcholine receptor subtypes involved incarbachol-induced HCO_3^- secretion inmouse duodenum in Vitro.2010

    • Author(s)
      Koji T, Masafumi K, Kento T, Eitaro A, Naoto K, Shusaku H
    • Organizer
      16^<th> World Congress on Basic and Clinical Pharmacology (Copenhagen, Denmark)
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2010-07-15
  • [Presentation] Role of nitric oxide in the regulatory mechanisms of gastroduodenal HCO 3^-recretion.2010

    • Author(s)
      Koji T
    • Organizer
      The 6^<th> International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2010-06-15
  • [Presentation] Activation of muscarinic acetylcholine receptor subtype 4 isessential for carbachol-inducedpepsinogen secretion in mice : relationto D cells/somatostatin.2010

    • Author(s)
      Ryoji K, Masashi Y, Kikuko A, Shinichi K, Koji T
    • Organizer
      American Gastroenterological Association
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-05-02
  • [Presentation] Role of calcium-sensing receptor (CaSR) on gastric acidsecretion in isolated mouse stomachs.2010

    • Author(s)
      Masafumi K、Shusaku H, Eitaro A, Shinichi K, Koji T
    • Organizer
      AmericanGastroenterological Association
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-05-02
  • [Presentation] Phosphodiesterase isozymes involved in regulatory mechanism of acid secretion in isolated mouse stomachs.2010

    • Author(s)
      Maya H、Sayaka O, Eitaro A, Shinichi K, Koji T
    • Organizer
      American Gastroenterological Association
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-05-02
  • [Presentation] Higher rate of acid-induced duodenal HCO_3^- secretion infemale than male rats : importance ofenhanced ASIC3 expression by estradiol.2010

    • Author(s)
      Masafumi K, Yumi O, Hironori T, Shusaku H, Eitaro A, Koji T
    • Organizer
      American Gastroenterological Association
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-05-02
  • [Presentation] Lubiprostone stimulates HCO_3^- secretion in isolated mouse stomachs in vitro through activation of prostaglandin EP1 receptors.2010

    • Author(s)
      Masafumi K, Shusaku H, Kento T, Koji T
    • Organizer
      American GastroenterologicalAssociation
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2010-05-02
  • [Presentation] 粘膜酸性化による十二指腸アルカリ分泌の増大における性差2010

    • Author(s)
      小山真史、大橋由美、高須賀洋徳、粟飯原永太郎、竹内孝治
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-03-16
  • [Presentation] 胃酸分泌の調節におけるホスホジエステラーゼ(PDE)アイソザイムの関与2010

    • Author(s)
      本田真弥、奥田さやか、出原千歳、加藤伸一、竹内孝治
    • Organizer
      第28回Cytoprotection研究会
    • Place of Presentation
      ホテルグランビア京都
    • Year and Date
      2010-03-05
  • [Presentation] 胃酸分泌におけるカルシウム感知受容体の関与2010

    • Author(s)
      高須賀洋徳、林周作、倉田直人、粟飯原永太郎、竹内孝治
    • Organizer
      第6回日本消化管学会総会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2010-02-19
  • [Presentation] 十二指腸アルカリ分泌におけるムスカリン受容体の関与2010

    • Author(s)
      小山真史、高橋健人、喜多一智、林周作、松井稔、竹内孝治
    • Organizer
      第6回日本消化管学会総会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2010-02-19
  • [Presentation] Effect of carbon monoxide/heme oxygenase on duodenal HCO_3^- secreton in rats.2010

    • Author(s)
      Hironori T、Masafumi K, Shusaku H, Eitaro A, Koji T
    • Organizer
      The 5^<th> Collaboration Meeting on GI Pharmacology co-sponsored by Kyoto Pharmaceutical University and Yonsei University
    • Place of Presentation
      京都薬科大学
    • Year and Date
      2010-02-04
  • [Presentation] Muscarinic acetylcholine receptor subtypes involved in carbachol-induced HCO_3^- recretion in mouse duodenum in vitro.2010

    • Author(s)
      Masafumi K、Kazutomo K, Kento T, Shusaku H, Shinichi K, Minoru M, Koji T
    • Organizer
      The 5^<th> Collaboration Meeting on GI Pharmacology co-sponsored by Kyoto Pharmaceutical University and Yonsei University
    • Place of Presentation
      京都薬科大学
    • Year and Date
      2010-02-04
  • [Book] Physiology of Gastrointestinal Tract2011

    • Author(s)
      Takeuchi, et al
    • Publisher
      Academic Press(in press)
  • [Book] Advanced Gas Biology for Medical and Clinical Practice2011

    • Author(s)
      Takeuchi, et al
    • Total Pages
      10
    • Publisher
      Karger Publisher
  • [Book] Advances Clin Chem2010

    • Author(s)
      Takeuchi K
    • Total Pages
      23
    • Publisher
      Academic Press

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Published: 2012-01-26   Modified: 2016-04-21  

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