1988 Fiscal Year Final Research Report Summary
Relationship between subtypes and cellular responses in muscarinic acetylcholine receptor system
| Project/Area Number |
62480120
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University Faculity of Medicine |
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Principal Investigator |
YOSHIDA Hiroshi Osaka University Faculity of Medicine, Professor, 医学部, 教授 (70028273)
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| 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)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Muscarinic acetylcholine receptor / Heart / Adenylate cyclasse / PIレスポンス |
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| 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.
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