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Signalling pathways and transporters involved in gastroduodenal bicarbonate secretion

Research Project

Project/Area Number 18590248
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

TAKEUCHI Koji  Kyoto Pharmaceutical University, Pharmacology and Experimental Therapeutics, Professor (00150798)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsgastroduodenal HCO_3^- secretion / endogeneous mediator / transport / sensory nerve / phosphodiesterase isozyme / carbonated beverages / carbonic anhydrease / cGMP / 輪送担体
Research Abstract

1. Coca-Cola topically applied to the mucosa for 10 min increased HCO_3^- secretion in both the stomach and the duodenum. The response in the duodenum was totally abolished by indomethacin and partially inhibited by acetazolamide, while the response in the stomach was inhibited by acetazolamide or indomethacin. Coca-Cola increased PGE_2 contents in both the stomach and the duodenum. These results suggest that Coca-Cola induces HCO_3^- secretion in both the stomach and duodenum, and the responses may be attributable to both the intracellular supply of HCO_3^-, by the aid of carbonic anhydrase, and endogenous PGs, probably related to the acidic pH of the solution.
2. PGE2 and NOR-3 increased HCO_3^- secretion in the mouse duodenum in vitro, and the response to PGE_2 was inhibited by both EP3 and EP4 antagonists, while that to NOR-3 was inhibited by methylene blue. Vinpocetine (PDE1 inhibitor) and cilostamide (PDE3 inhibitor) potentiated the response to PGE2. By contrast, the stimulatory action of NOR-3 was significantly potentiated by vinpocetine but not cilostamide. These results suggested that PDE1 and PDE3 are involved in the regulation of duodenal HCO_3^- secretion and that the response to PGE_2 is associated with both PDE1 and PDE3, while the response to NO is mainly modulated by PDE1.
3. Both NOR-3 and 8-brcGMP dose-dependently stimulated HCO_3^- secretion, and the response to NOR-3 was inhibited by methylene blue. Likewise, the secretion induced by NOR-3 or 8-br-cGMP was attenuated by ONO-8711 (EP1 antagonist) as well as indomethacin and potentiated by both vinpocetine and zaprinast. NOR-3 increased the mucosal PGE_2 content in a methylene blue-inhibitable manner. These results suggest that NO stimulates gastric HCO_3^- secretion mediated intracellularly by cGMP and modified by both PDE1 and PDE5, and this response is finally mediated by endogenous PGE_2 via the activation of EP1 receptors.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (32 results)

All 2007 2006 2005

All Journal Article (31 results) (of which Peer Reviewed: 10 results) Book (1 results)

  • [Journal Article] Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats2007

    • Author(s)
      Eitaro Aihara, Yoko Nomura, Yoko Sasaki, Fumitaka Ise, Kazutomo Kita and Koji Takeuchi
    • Journal Title

      Life Sci. 80

      Pages: 2446-2453

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phosphodiesterase isozymes involved in regulation of HCO_3^- secretion in isolated mouse duodenum in vitro2007

    • Author(s)
      Masamune Hayashi, Kazutomo Kita, Yumi Ohashi, Eitaro Aihara and Koji Takeuchi
    • Journal Title

      Biochem.Pharmacol. 74

      Pages: 1507-1513

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Stimulatory effect of Coca-Cola on gastroduodenal HCO_3^- secretion in rats2007

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Fumitaka Ise, Kazutomo Kita and Koji Takeuchi
    • Journal Title

      Inflammopharmacology 15

      Pages: 223-228

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Stimulatory action of sparkling water on gastroduodenal HCO_3^- secretion in rats2007

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Fumitaka Ise and Koji Takeuchi
    • Journal Title

      Ulcer Research 34

      Pages: 15-18

    • NAID

      10019501702

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats.2007

    • Author(s)
      Eitaro Aihara, Yoko Nomura, Yoko Sasaki, Fumitaka Ise, Kazutomo Kita, Koji Takeuchi
    • Journal Title

      Life Sci. 80

      Pages: 2446-2453

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phosphodiesterase isozymes involved in regulation of HCO_<3-> secretion in isolated mouse duodenum in vitro.2007

    • Author(s)
      Masamune Hayashi, Kazutomo Kita, Yumi Ohashi, Eitaro Aihara, Koji Takeuchi
    • Journal Title

      Biochem. Pharmacol. 74

      Pages: 1507-1513

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Stimulatory effect of Coca-Cola on gastroduodenal HCO_<3-> secretion in rats.2007

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Fumitaka Ise, Kazutomo Kita, Koji Takeuchi
    • Journal Title

      Inflammopharmacology 15

      Pages: 223-228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Stimulatory action of sparkling water on gastroduodenal HCO_3-secretion in rats.2007

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Fumitaka Ise, Koji Takeuchi
    • Journal Title

      Ulcer Research 34

      Pages: 15-18

    • NAID

      10019501702

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Stimulatory effect of Coca-Cola on gastroduodenal HCO_3 secretion in rats2007

    • Author(s)
      Sasaki, et. al.
    • Journal Title

      Inflammopharmacology 15

      Pages: 223-228

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats2007

    • Author(s)
      Aihara, et. al.
    • Journal Title

      Life Sciences 80

      Pages: 2446-2453

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy)benzamido)ethyl)benzoic acid (CJ-42794),a selective antagonist of prostaglandin E receptor subtype 4,0nulcerogenic and healing responses in rat gastrointestinal mucosa2007

    • Author(s)
      Takeuchi, et. al.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 322

      Pages: 903-912

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphodiesterase isozymes involved in regulation of HCO_3 secretion in isolated mouse duodenum in vitro2007

    • Author(s)
      Hayashi, et. al.
    • Journal Title

      Biochemical Pharmacology 74

      Pages: 1507-1513

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 胃アルカリ分泌におけるボスポジエステラーゼの役割2007

    • Author(s)
      野村, 他
    • Journal Title

      Ulcer Research 34

      Pages: 11-14

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 炭酸水による胃および十二指腸におけるアルカリ分泌促進2007

    • Author(s)
      佐々木, 他
    • Journal Title

      Ulcer Research 34

      Pages: 15-18

    • Related Report
      2007 Annual Research Report
  • [Journal Article] カプサイシン誘起胃アルカリ分泌の調節機序2007

    • Author(s)
      粟飯原, 他
    • Journal Title

      消化管運動 9

      Pages: 7-9

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Stimulatory effect of Coca-Cola on gastro duodenal HCO_3 secretion in rats2007

    • Author(s)
      Sasaki et al.
    • Journal Title

      Inflammopharmacology 15(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct mechanisms of acid-induced HCO_3^- secretion in normal and slightly permeable stomachs2006

    • Author(s)
      Eitaro Aihara, Yoko Sasaki, Fumitaka Ise, Kazutomo Kita, Yoko Nomura and Koji Takeuchi
    • Journal Title

      Am.J.Physiol. 291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Involvement of cyclooxygenase-1,prostaglandin E_2 and EP1 receptors in acid-induced HCO_3^- secretion in stomach2006

    • Author(s)
      Koji Takeuchi, Eitaro Aihara, Yoko Sasaki, Yoko Nomura and Fumitaka Ise
    • Journal Title

      J.Physiol.Pharmacol. 57

      Pages: 661-676

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Stimulation by dradykinin of HCO_3^- secretion in rat gastroduodenal mucosa2006

    • Author(s)
      Eitaro Aihara, Masamune Hayashi, Yoko Nomura, Shinichi Kato and Koji Takeuchi
    • Journal Title

      Med.Sci.Monit. 12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gastric HCO_3^- secretion induced by mucosal acidification:different mechanisms depending on acid concentration2006

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Masamune Hayashi and Koji Takeuchi
    • Journal Title

      Ulcer Research 33

      Pages: 189-191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mucosal protective action of prostaglandin E_22006

    • Author(s)
      Koji Takeuchi.
    • Journal Title

      the alimentary tract and EP receptor subtypes.In "Discoveries in Gastroenterology"., Akademiai Kiado,Budapest

      Pages: 585-626

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mucosal protective action of prostaglandin E_2 in the alimentary tract and EP receptor subtypes.2006

    • Author(s)
      Koji Takeuchi
    • Journal Title

      In Discoveries in Gastroenterology , ed. : Gyula Mozsik,(Akademiai Kiado, Budapest)

      Pages: 585-626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct mechanisms of acid-induced HCO_<3-> secretion in normal and slightly permeable stomachs.2006

    • Author(s)
      Eitaro Aihara, Yoko Sasaki, Fumitaka Ise, Kazutomo Kita, Yoko Nomura, Koji Takeuchi
    • Journal Title

      Am. J. Physiol. 291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Involvement of cyclooxygenase-1, prostaglandin E_2 and EP1 receptors in acid-induced HCO_<3-> secretion in stomach.2006

    • Author(s)
      Koji Takeuchi, Eitaro Aihara, Yoko Sasaki, Yoko Nomura, Fumitaka Ise
    • Journal Title

      J. Physiol. Pharmacol. 57

      Pages: 661-676

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Stimulation by bradykinin of HCO_<3-> secretion in rat gastroduodenal mucosa.2006

    • Author(s)
      Eitaro Aihara, Masamune Hayashi, Yoko Nomura, Shinichi Kato, Koji Takeuchi
    • Journal Title

      Med. Sci. Monit. 12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gastric HCO_<3-> secretion induced by mucosal acidification : different mechanisms depending on acid concentration.2006

    • Author(s)
      Yoko Sasaki, Eitaro Aihara, Masamune Hayashi, Koji Takeuchi
    • Journal Title

      Ulcer Research 33

      Pages: 189-191

    • NAID

      10018262464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct mechanisms of acid-induced HCO_3 secretion in normal and slightly permeable stomachs2006

    • Author(s)
      Aihara et al.
    • Journal Title

      American Journal of Physiology 291

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Involvement of cyclooxygenase-1, prostaglandin E_2 and EP1 receptors in acid-induced HCO_3 secretion in stomach2006

    • Author(s)
      Takeuchi et al.
    • Journal Title

      Journal of Physiology and Pharmacology 56

      Pages: 661-676

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mechanisms underlying capsaicin-stimulated HCO_<3-> secretion in the stomach : comparison with mucosal acidification.2005

    • Author(s)
      Eitaro Aihara, Masamune Hayashi, Yoko Sasaki, Atsushi Kobata, Koji Takeuchi
    • Journal Title

      J. Pharmacol. Exp. Ther. 315

      Pages: 423-432

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gastric HCO_<3-> secretion induced by mucosal acidification : different mechanisms depending on acid concentration.2005

    • Author(s)
      Eitaro Aihara, Masamune Hayashi, Yoko Sasaki, Koji Takeuchi
    • Journal Title

      Inflammopharmacology 13

      Pages: 179-190

    • NAID

      10018262464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of prostaglandin E receptor subtypes in gastroduodenal HCO_<3-> secretion.2005

    • Author(s)
      Koji Takeuchi, Eitaro Aihara, Masamune Hayashi, Yoko Sasaki
    • Journal Title

      Medicinal Chemistry 1

      Pages: 395-403

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] DDW 2007 Session Handout Book2007

    • Author(s)
      Takeuchi
    • Publisher
      米国消化器病学会
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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