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Relationship between subtypes and cellular responses in muscarinic acetylcholine receptor system

Research Project

Project/Area Number 62480120
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionOsaka University Faculity of Medicine

Principal Investigator

YOSHIDA Hiroshi  Osaka University Faculity of Medicine, Professor, 医学部, 教授 (70028273)

Co-Investigator(Kenkyū-buntansha) 樋口 宗史  大阪大学, 医学部, 助手 (30150337)
WATANABE Yasuhiro  Osaka University Faculity of Medicine, Asst. Prof., 医学部, 講師 (90127324)
UCHIDA Shuji  Osaka University Faculity of Medicine, Assoc. Prof., 医学部, 助教授 (90028639)
大杉 武  大阪大学, 医学部, 助手 (50176880)
中広 全延  大阪大学, 医学部, 助手 (00172388)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsMuscarinic acetylcholine receptor / Heart / Adenylate cyclasse / PIレスポンス / アテニレートシクラーゼ / Pエレスポンス / ムスカリニックレセプター / PI代謝
Research Abstract

Four subtypes (M1-M4) in muscarinic receptors (mACh-R) were discovered by the method of gene technology. But, three of them are distinguishable pharmacologi-cally. That is M1 subtype, a neuronal maCh-R, M2, a cardiac maCh-R and M3, maCh-R in other peripheral tissues.
Cardiac maCh-R (M2 subtype) are thought to consist of a single species of receptor protein. We analyzed the binding characteristics of muscarinic agonists to cardiac maCh-R by computer-assisted least square method. The results showed that cardiac maCh-R consist of two subclasses, both regulated by GTP binding proteins. We called them M2 with higher affinity for the agonists and M2 with the lower affinity. M2 couples with inhibition of adenylate cyclase and M2 with activation of PI turnover.
Cardiac tissue are reported to contain only M2 mRMA. Then, what makes dif-ferences between M2 and M2 ? It is possible that M2 and M2 come from dif-ferent modification of receptor proteins, such as phosphorylation, methylation, association with other protein or polymerization. We are now working on clarify-ing this problem.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] S.,Uchida: Biomedical Res.8(Suppl). 157-161 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.,Mizushima: Eur.J.Pharmacol.135. 403-409 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] X.M.,Zhou: Europ.J.Pharmacol.154. 229-236 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.,Watanabe: FEBS Letters. 236. 372-375 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.,Mizushima: Europ.J.Pharmacol.in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] X.M. Zhou: "The SH-H subgroup of cardiac M_2 receptors (M_2 ) inhibits adenulate cyclase activity." Europ. J. Pharmacology. 154. 229-236 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y. Watanabe: "Effect of phosphorylation of inhibitory GTP-binding protein by cyclic AMP-dependent protein kinase on its ADP-ribosylation by pertussis toxin, islet-activating protein." FEBS Letters. 236. 372-375 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A. Mizushima: "The H-L subgroup of guinea-pig cardiac M_2 receptors (M_2 ) regulates formation of inositol phosphates." European J. Pharmacol.in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] X.M.Zhou: Europ.J.Pharmacol.154. 229-236 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Watanabe: FEBS Letters. 236. 372-375 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] A.Mizushima: Europ.J.Pharmacol.

    • Related Report
      1988 Annual Research Report
  • [Publications] X.-M.Zhou: European J.Pharmacology.

    • Related Report
      1987 Annual Research Report
  • [Publications] S.Uchida,: Bisdnedical J.

    • Related Report
      1987 Annual Research Report
  • [Publications] 水島淳: 実験医学. 5. 484-488 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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