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ROLES OF PROTEASE-ACTIVATED RECEPTORS IN THE ALIMENTARY SYSTEMS : PARTICIPATION IN THE MODULATION OF FUNCTIONS IN THE SALIVARY GLANDS, PANCREAS AND SMALL INTESTINE

Research Project

Project/Area Number 11672283
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKINKI UNIVERSITY

Principal Investigator

KAWABATA Atsufumi  KINKI UNIVERSITY, DEPT.OF PATHOPHYSIOLOGY, FAC.OF PHARMCEUT.SCI, 薬学部, 助教授 (20177728)

Co-Investigator(Kenkyū-buntansha) KURODA Ryotaro  KINKI UNIVERSITY, DEPT.OF PATHOPHYSIOLOGY, FAC.OF PHARMCEUT.SCI., PROFESSOR, 薬学部, 教授 (10161803)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsprotease-activated receptor / protease / PAR / gastrointestinal motility / salivation / pancreatic secretion / 消化器 / 唾液 / 膵液 / アミラーゼ / 小腸運動 / アパミン / カルシウムチャネル / カリウムチャネル / トロンビン / トリプシン
Research Abstract

Protease-activated receptors (PARs), G protein-coupled seven trans-membrane domain receptors activated by certain proteases such as thrombin, trypsin and tryptase, play various physiological/pathophysiological roles especially during tissue injury or inflammation. We investigated the physiological roles of PARs in the alimentary systems.
Activation of PAR-1 produced apamin-sensitive relaxation followed by contraction in the isolated rat duodenal smooth muscle. PAR-2 activation elicited only contraction. PAR-4 produced no response. The PAR-1-mediated contraction was largely dependent on increased sodium permeability and activation of L-type calcium channels, and in part on activation of tyrosine kinase, protein kinase C and PI3 kinase.
We next detected mRNA for PAR-2 in the salivary glands and pancreas. Then, activation of PAR-2 in vivo markedly augmented exocrine secretion in both the tissues.
In conclusion, our study demonstrates that PARs present in the small intestine, salivary glands and pancreas modulate various physiological functions, predicting that PARs could be targets for drug development.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kawabata,A., et al.: "Modulation by protease-activated receptors of the rat duodenal motility in vitro : possible mechanisms underlying the evoked contraction and relaxation"British Journal of Pharmacology. 128. 865-872 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata,A. et al.: "Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smooth muscle"Life Sciences. 67. 2521-2530 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata,A. et al.: "Protease-activated receptor-2 (PAR-2) : regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice"British Journal of Pharmacology. 129. 1808-1814 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata,A. et al.: "Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland"Biochemical and Biophysical Research Communications. 270. 298-302 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Modulation by protease-activated receptors of the rat duodenal motility in vitro : possible mechanisms underlying the evoked contraction and relaxation"Br.J.Pharmacol.. 128. 865-872 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smooth muscle"Life Sci.. 67. 2521-2530 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Protease-activated receptor-2 (PAR-2) : regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice"Br.J.Pharmacol.. 129. 865-872 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland"Biochem.Biophys.Res.Commun.. 270. 298-302 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawabata,A. et al.: "Determination of mucin in salivary glands using sialic acid as the marker by high performance Liquid chromatography with fluorometric detection"Anal.Biochem.. 283. 119-121 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawabata,A. et al.: "Characterization of the protease-activated receptor-1-mediated contraction and relaxation in the rat duodenal smooth muscle"Life Sci.. 67. 2521-2530 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawabata,A. et al.: "Protease-activated receptor-2-(PAR-2) : regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice"Br.J.Pharmacol.. 129. 1627-1632 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawabata,A. et al.: "Activation of protease-activated receptor-2 (PAR-2) triggers mucin secretion in the rat sublingual gland"Biochem.Biophys.Res.Commun.. 270. 298-302 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawabata,A.,Kuroda,R,Nishikawa,H.& Kawai,K.: "Modulation by protease-activated receptors of the rat duodenal motility invitro:possible mechanisms underlying the evoked contraction and relaxation"Br.J.Pharmacol.. 128. 865-872 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata,A.and Kuroda,R.: "Protease-activated receptor (PAR),a novel family of G protein-coupled seven transmembrane domain receptors:activation mechanisms and physiological rdes"Jpn.J.Pharmacol.. 82. 171-175 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata,A.,Nishikawa,H.Kuroda,R.,Kawai,K.,Hollenberg,M.D.: "Proteinase-activated receptor-2:regulation of salivary and pancreatic exocrine secretion in vivo in rats and mice"Br.J.Pharmacol.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata,A.,Morimoto,N.,Nishikawa,H.,Kuroda,R.,Oda,Y.and Kakehi,K.: "Activation of protease-activated receptor-2 triggers mucin secretion in the rat sublingual gland"Biochem.Biophys.Res.Commun.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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