| Project/Area Number |
09044276
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Biological pharmacy
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
KIMURA Ikuko Faculty Of Pharmaceutical Science, Toyama Medical and Pharmaceutical University Associate Professor, 薬学部, 助教授 (70019131)
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| Co-Investigator(Kenkyū-buntansha) |
CHANGEUX J?P パスツール研究所, 教授
DEZAKI Katsuya Japan Society for the Promotion of Sciences, Research Fellow, 特別研究員
NOJIMA Hiroshi Facutly Of Pharmaceutical Science, Toyama Medical and Pharmaceutical University Associate Professor, 薬学部, 助手 (50208344)
HAGINO Nobuyoshi University of Texas San Antonio, Professor, サンアントニオ校・健康科学センター, 教授
CHANGEUX Jean-Pierre Institut Pasteur, Professor
木村 正康 テキサス大学サンアントニオ校, 健康科学センター, 教授
CHANGEUX J.ー パスツール研究所, 神経分子生物学, 教授
HAGINO Nobuy テキサス大学, サンアントニオ・健康科学センター, 教授
恒枝 宏史 パスツール研究所, 神経分子生物学, 客員研究員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1997: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | nicotine / β2-knock out mouse / substantia nigra pars compacta / α7-subunit / methyllycaconitine / neuronal type-nicotinic acetylcholine receptor / dopaminergic neuron / receptor activity-modulating intracellular calcium / β2ノックアウトマウス / 中脳黒質 / methyllycaconitine / Ca^<2+> / アセチルコリン受容体チャネル電流 / RAMIC / 脱感作 / α-bungarotoxin |
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| Research Abstract |
Desensitizing interaction between muscle (M)-and neuronal (N)-types of nicotinic acetylcholine receptors (nAChR) occurs through menthyllycaconitine (MLA)-sensitive slow CaィイD12+ィエD1 mobilization (RAMIC : receptor activity-modulating intracellular calcium) in neuromuscular synapse. To elucidate functional roles of N-nAChR in brain and identify the N-nAChR subunit regulating M-nAChR in neuromuscular synapse, we assessed the intracellular CaィイD12+ィエD1 level by imaging fura-2-loaded cells in brain slices (substantia nigra pars compacta) and in single skeletal muscle cells (flexor digitorum brevis) of mice lacking the nAChRβ2-subunit. 1. Neuromuscular synapse : Either RAMIC induced by cytisine (20μM) and Ach (3μM) or desensitization in opening frequency of ACh-activated channel current was observed β2-mutant (-/-) mice in the same manner as in β2(+/+) wildtype sibling mice. 2. Substantia nigra pars compacta : Superfusion with nicotine (10-100μM) caused a long-lasting rise of intracellular CaィイD12+ィエD1 level in an extracellular CaィイD12+ィエD1-dependent manner in wild-type mice but not in β2(-/-) mutant mice. Alpha 7-subunit-selective agonist choline (10mM) caused a MLA-sensitive increase of intracellular CaィイD12+ィエD1 level both in wild-type and β2(-/-) mutant mice. In nigral dopaminergic neurons, nicotine can elicit CaィイD12+ィエD1 mobilization via two distinct mechanisms of either activation of β2- or of α7-subunit-containing nAChR. In neuromuscular synapse, β2-subunit is less involved to produce a MLA-sensitive RAMIC. I
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