| Project/Area Number |
12557216
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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 |
医薬分子機能学
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
KIRINO Yutaka The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (10012668)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Ryota The University of Tokyo, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (40334338)
WATANABE Satoshi The University of Tokyo, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (80302610)
KAWAHARA Shigenori The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (10204752)
KAWAKAMI Yoshiyuki Eisai Corporation Tsukuba Laboratory, Chief Research Scientist, 筑波研究所, 主幹研究員
SATO Kazunori Fukuoka women's University, Faculty of Humanities, Professor, 人間環境学部, 教授 (10326473)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | Calcium channel / Autoimmune disease / Lambert-Eaton myasthenic syndrome / 神経筋接合部 / マウス / ダウンレギュレーション / internalization / モデル動物 |
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| Research Abstract |
1. Atropin, a non-selective mAChR antagonist, reduced both mepp amplitude and frequency. By using mAChR-subtype specific knockout mice, it proved that M1 and M3 mAChR are required for transmitter release at NMJ.
2. We analyzed whether anti-P/Q-type Ca channel antibody or antisera from LEMS patients reduce the amount of the channel or the Ca influx from the P/Q-type Ca channels expressed stably on the surface of HEK293 cells. Here we successfully generated anti-P/Q-type Ca channel antibody, and showed mat it down-regulated the amount of the channel. It also reduced depolarization-dependent Ca influx.
3. It has been thought that LEMS is caused by the reduction in the amount of Ach released from presynaptic terminals in NMJ. To test this, we analyzed the effects of AChE inhibitor E2020 applied in the presence and the absence of K^+ channel blocker 4-aminopyridine. Surprisingly, the effect of the treatment by both of these drugs were not additive, but synergetic against the NMJ transmission.
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