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Study on roles for PAR-2, a G protein-coupled receptor, in acute inflammation

Research Project

Project/Area Number 13672405
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, Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20177728)

Co-Investigator(Kenkyū-buntansha) KURODA Ryotaro  Kinki University, Pharmaceutical Sciences(retired in March,2003), Professor, 薬学部(H15年3月退職), 教授 (10161803)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsPAR-2 / blood vessel / endotoxin / inflammation / protease / sensory neuron / pain / salivary gland / PAR / 内臓痛 / 肺上皮細胞 / プロスタグランジン / EDHF / 耳下腺 / Fos / 唾液 / 血圧
Research Abstract

The protease-activated receptor(PAR), a G protein-coupled receptor family consists of 4 members, and modulates a variety of physiological functions upon activation in response to inflammation, tissue injury and hemorrhage. The present study investigated the roles and changes of PARs, particularly PAR-2, in acute inflammation.
We first studied changes of sensitivity of PAR-2 present in the salivary glands in mice treated with lipopolysaocharide, and found that PAR-2 might be tonically activated and desensitized by endogenous PAR-2 activators under systemic inflammatory conditions. Endogenous PAR activators including thrombin, factors VII and X, mast cell tryptase might become activated and/or accessible to tissues in septic shock. Vasodilation by these enzymes via PAR activation might contribute to development of hypotension caused by septic shock. In this context, we examined the mechanisms underlying the vascular contraction and relaxation caused by PAR activation. We then investigated roles of PARs, known to be present in capsaicin-sensitive sensory neurons, in inflammatory visceral pain and parotitis-related pain. Our data provide novel evidence that PARs, particularly PAR-2,is involved in inflammation and related pain, circulatory disturbance, etc.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kawabata, A.et al.: "Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo"Naunyn-Schmiedeberg's Arch.Pharmacol.. 364. 281-284 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats"Br.J.Pharmacol.. 140. 247-254 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 川畑篤史, 河尾直之: "Protease-activated receptorsと炎症"BIO Clinica. 18. 551-555 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A.et al.: "Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery"Cardiovasc.Res.. 61. 683-692 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawao, Ikeda, Kitano, Kuroda, Sekiguchi, Kataoka, Kamanaka, Kawabata, A.: "Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2"J.Pharmacol.Sci.. 94. 277-285 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A. et al.: "Lipopolysaocharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo"Naunyn-Schmiedeberg's Arch.Pharmacol.. 364. 281-284 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A. et al.: "Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats"Br.J.Pharmacol.. 140. 247-254 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A., Kawao, N.: "Protease-activated receptors and inflammation"Cardiovasc.Res.. 18. 551-555 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A. et al.: "Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery"BIO Clinica.. 61. 683-692 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawao, N., Ikeda, H., Kitano, T., Kuroda, R., Sekiguchi F., Kataoka, K., Kamanaka, Y., Kawabata, A.: "Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2"J.Pharmacol.Sci.. 94. 277-285 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawabata, A. et al.: "Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery"Cardiovasc. Res.. 61. 683-692 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawabata, A. et al.: "Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats"Br.J.Pharmacol.. 140. 247-254 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 川畑篤史, 河尾直之: "Protease-activated receptorsと炎症"BIO Clinica. 18. 551-555 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawao, N. et al.: "Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2"J.Pharmacol.Sci.. 94(In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawabata, A. et al.: "Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo"Naunyn-Schmiedeberg's Arch. Pharmacol.. Vo.364. 281-284 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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