| Project/Area Number |
13670105
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
OHKUMA Seitaro Kawasaki Medical School, Dept. of Pharmacology, Professor, 医学部, 教授 (30152086)
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| Co-Investigator(Kenkyū-buntansha) |
KATSURA Masashi Kawasaki Medical School, Dept. of Pharmacology, lecturer, 医学部, 助手 (80204452)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | β-adrenoceptors / up-regulation / nadolol / [3H] CGP-12177 binding / adenylate cyclase / cerebrocortical neurons / β-arrestin / 3H]CGP-12177結合 / [^3H]CGP-12177結合 |
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| Research Abstract |
In this research project, we attempted to investigate alterations in intracellular signal transduction systems coupling to β-adrenoceptors (β-AR) in association with β-AR up-regulation
At first, we confirmed that mouse cerebral cortical neurons in primary culture used had both β1- and β2-AR coupling to Camp generating system. Sustained exposure to nadolol induced a maximal increase of [3H] CGP-12177 binding after 6 hr of the exposure and increased both β-AR expressions on neuronal membrane. On the other hand, increased expression of mRNA of these eceptor was found 12 hr after the exposure. The increased receptor expression on neuronal membrane was due to increased translocation of receptor proteins from cytosol to membrane, and synthesis of receptor proteins did not participate in these events. After the expression of receptor mRNA increased, the expendent on synthesis of the proteins
In association with β-AR up-regulation, forskolin-evoled formation of Camp increased. Among adenylate cyclase (AC) isozymes present in the neurons, only type I was found to increase significantly accompanying with β-AR up-regulation. In addition, β-AR up-regulation
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