| Project/Area Number |
60480127
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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 |
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Principal Investigator |
YOSHIDA Hiroshi Osaka University School of Medicine, Professor, 医学部, 教授 (70028273)
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| Co-Investigator(Kenkyū-buntansha) |
OSUGI Takeshi Osaka University school of Medicine, Assistant Prof., 医学部, 助手 (50176880)
NAKAHIRO Masanobu Osaka University School of Medicine, Assistant Prof., 医学部, 助手 (00172388)
WATANABE Yasuhiro Osaka University School of Medicine, Assistant Prof., 医学部, 助手 (90127324)
UCHIDA Shuji Osaka University School of Medicine, Associate Prof., 医学部, 助教授 (90028639)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | muscarinic acetylcholine receptor and tis subtypes / mAchR(ムスカリン様アセチルコリン受容体) / 記憶 |
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| Research Abstract |
[ <I> ] Mechanisms of disensitization(D).
Desensitization caused by exposure to agonists is usually divided into short-term, long-term and also into homologous- and heterologous-desensitization.
(1) In case of long-term, homologous D. amount of mAChR was decreased. This decrease was caused by acceleration of degradation of the receptor by processes of endocytosis and internalization.
(2) In case of short-term homogolous D. amount of mAChR did not changed, but affinity of agonists to the receptor decreased even in presence and absence of enough amount of GTP&S.
(3) Heterologous D. was observed when NG108-15 cells were exposed to bradykinin. This subsensitivity seemed to come from certain change in GTP-binding protein - <PIP_2> specific phospholipase C complex.
[ <II> ] Subtypes of mAChR in cardiac muscle
Binding of antagonist to mAChR in cardiac muscle was monophasic, but binding of agonist was not monophasic. Accordingly, we analyzed the binding site of agonist on mAChR and found that there are two kinds of binding sites having different affinity to agonist and both binding sites are regulated by GTP-binding protein and SH-reagent. Then, it was found that the higher affinity binding site is coupled with inhibitory effect on adenylate cyclase.
[ <III> ] Role of mAChR in leaning and memory.
An irreversible muscarinic antagonist, propylbenzilylcholine mustard (PrBCM), was micro injected into the brain cortex and effect of the injection on memory was examined by passive avoidance.
<i> ) Injection of PrBCM into the frontal and parietal cortex caused loss of memory, but not into the occipital cortex.
<ii> ) The injection impaired the acquisition and recalling phases, but the retention phase was kept almost intact.
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