| Project/Area Number |
09480236
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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 | 一般 |
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| Research Field |
神経・脳内生理学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
YAWO Hiromu Graduate School of Medicine, Tohoku University, Professor, 大学院・医学系研究科, 教授 (00144353)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Takaaki Graduate School of Medicine, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (80292209)
UMEMIYA Masashi Graduate School of Medicine, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (50271911)
KAWA Kazuyoshi Graduate School of Medicine, Tohoku University, Associate Professor, 大学院・医学系研究科, 助教授 (70125839)
ISHII Kuniaki School of Medicine, Yamagata University, Associate Professor, 医学部, 助教授 (10184459)
SAHEKI Shuichi Health Administration Center, Ehime University, Professor, 保健管理センター, 教授 (80145078)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1997: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | noradrenaline / adrenergic receptor / guanylyl cyclase / cGMP / protein kinase G / phosphorylation / transmitter release / presynaptic terminal / サイクリックGMP(cGMP) / 一酸化窒素 / プロテインキナーゼ / 開口放出 / シナプス可塑性 / カルシウム |
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| Research Abstract |
We have previously reported that norepinephrine (NE) induces a sustained potentiation of transmitter release in the chick ciliary ganglion through a mechanism pharmacologically distinct form any known adrenergic receptors. Here we report that the adrenergic potentiation of transmitter release was enhanced by a phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and by zaprinast, an inhibitor of cGMP-selective phosphodiesterase. Exogenous application of the membrane-permeable cGMP, 8Br-cGMP, potentiated the quantal transmitter release and, after potentiation, the addition of NE was no longer effective. On the other hand, 8Br-cAMP neither potentiated the transmitter release nor occluded the NE-induced potentiation. The NE-induced potentiation was blocked by neither NO synthase inhibitor nor NO scavenger. The quantal transmitter release was not potentiated by NO donors, e.g. sodium nitroprusside (SNP). The NE-induced potentiation and its enhancement by IBMX was antagonized by two inhibitors of protein kinase G (PKG), Rp-8pCPT-cGMPS and KT5823. As with NE-induced potentiation, the effects of 8Br-cGMP on both the resting [CaィイD12+ィエD1]ィイD2iィエD2 and the action potential-dependent increment of [CaィイD12+ィエD1]ィイD2iィエD2 (ΔCa) in the presynaptic terminal were negligible. The reduction of the paired-pulse ratio of EPSC is consistent with the notion that the NE/cGMP-dependent poteitiation of transmitter release was due mainly to an increase of the exocytotic fusion probability. These results indicate that NE binds to a novel adrenergic receptor that activate guanylyl cyclase and that accumulation of cGMP activates PKG, which may phosphorylate a target protein involved in the exocytosis of synaptic vesicles.
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