| Project/Area Number |
08557147
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
OHKUMA Seitaro Kawasaki Medical School・Dept of Pharmacol.Professor, 医学部, 教授 (30152086)
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| Co-Investigator(Kenkyū-buntansha) |
KATSURA Masashi Kawasaki Medical School・Dept.of Pharmacol Instructor, 医学部, 助手 (80204452)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | beta-adrenocentors / neurons / up-regulation / protooncogenes / nitric oxide / GABA / Ca^<2+> channels |
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| Research Abstract |
Regulatory mechanisms for exoression of neurotransmitter receptors, especially beta-adrenergic receptors ( beta-AR), were investigated by measuring [^3H] CGP-12177 binding to the particulate fraction from mouse cerebral cortical neurons and mRNAs of beta1-and beta2-AR in neurons exposed to nadolol, an antagonist of beta-AR.Nadolol exposure induced rapid increase in the binding within 12 hrs and the binding attained its plateau after 24 hrs of the exposure. When measuring [^3H] CGP-12177 binding in the presence of each antagonist for beta2-and beta1-AR,the bindings significantly increased, indicating that the bindings to both beta1-and beta2-AR increased. Scatchard analysis revealed that this increase in the binding was due to Bmax balue without any changes in Kd value. mRNAs for both beta-AR subtypes increased significantly 24 hrs after the exposure, suggesting two distinct processers, increasing processer of receptor number with and without increase in mRNA.After 15 min and 1 hr of the exposure significant and transient increases in zif286 and c-fos mRNAs were observed. Induction of antisense for zif286 into the neurons before the exposure to nadolol abolished nadolol-induced increase in [^3H] CGP-12177 binding. These results indicate that the expression of zif286 plays a significant role in the expression of beta-AR upregulation. Inaddition, released of GABA release mechanisms by nitric oxide (NO) were investigated. Both materials induced increases in GABA release both dependent on Ca^<2+> and independent of Ca^<2+>. The latter type of release was the reverse process of Na^+-dependent GABA transport system. The increased influx Ca^<2+> of by NO is clarified to be caused by activation of L-and P/Q-typed voltage-dependent Ca^<2+> channels.
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