| Project/Area Number |
63060006
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Research Institution | Tokyo Metropolitan Institute for Neurosciences |
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Principal Investigator |
KAWAI Nobufumi 東京都神経科学総合研究所, 病態神経生理学研衆室, 参事研究員 (00073065)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Kennichi 東京大学, 薬学部, 助手 (40192265)
SHIMAZAKI Kuniko 東京都神経科学総合研究所, 病態神経生理学研究室, 研究員 (40142153)
MIWA Akiko 東京都神経科学総合研究所, 病態神経生理学研究室, 研究員 (60142155)
NAKAJIMA Terumi 東京大学, 薬学部, 教授 (50012597)
佐原 資謹 東京都神経科学総合研究所, 流動研究員 (40206008)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥181,000,000 (Direct Cost: ¥181,000,000)
Fiscal Year 1990: ¥34,000,000 (Direct Cost: ¥34,000,000)
Fiscal Year 1989: ¥57,000,000 (Direct Cost: ¥57,000,000)
Fiscal Year 1988: ¥90,000,000 (Direct Cost: ¥90,000,000)
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| Keywords | Glutamate Receptor / Glutamic acid / JSTX / Spider Toxin / GTP Binding Protein / Cerebellum / Hippocampus / Brain Ischemia / グルタミン酸レセプター / アビジン・ビオチン / 1-ナフチルアセチルスペルミン / 標識化クモ毒素 / アフィニティーカラム |
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| Research Abstract |
Using spider toxins isolated from the venom of spider (Nephila clavata), glutamate receptors in crustacean neuromuscular synapse and in the mammalian brain were characterized.
1. The structure activity relationships of synthesized analogs of the spider toxin revealed that 2, 4-dihydroxyphenylacetyl asparagine in the toxin structure was responsible for blocking action while remaining part containing a polyamine was related to the agonist binding site with the polycationic part enhancing the toxic activity.
2. Using autoradiography, ^<125>I JSTX-3 was found to bind at the lobster neuromuscular synapse. Histochemical study utilizing the interaction of biotinylated JSTX-3 with avidin showed specific binding of the toxin in rat cerebellum and hippocampus.
3. JSTX-3 binding protein was purified from rat and bovine brain by affinity chromatography. Reconstitution experiment of the purified protein into lipid bilayer membrane showed glutamate-associate single channel activities by patch clamp recordings
4. A novel type of glutamate receptor (Glutamate B) was found in the presynaptic membrane of the lobster neuromuscular synapse.
GlutamateB receptor coupled to G-prein activating K+ current which regulate the transmitter release in the nerve terminals
5. Membrane potential changes were studied in the hippocampal neurons of gerbil following brief occlusion of carotid arteries. 1-2 days after ischemia, abnormal potential changes were observed in CA1 pyramidal neurons. The changes could be responsible for disturbed Ca2+ homeostasis.
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