Regulation of glutamate neurotransmission by endogenous Zn^<++>

内源性 Zn 对谷氨酸神经传递的调节^< >

• 批准号: 02454136
• 负责人: BABA Akemichi
• 金额: $ 3.78万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454136/
• 关键词: Glutamate; Zn^<++>; NMDA receptor; Protein kinase C; astrocyte; swelling; Zn^<++>; アストロサイト; Swelling; 亜鉛イオン; protein kinase C; swelling; NMDA受容体; プロテインキナ-ゼC

1.Effect of L-glutamate on Zn^<2+> binding protein: We found a Zn^<2+> binding protein in cytosolic fraction of rat hippocampus. L-glutamate and its analogues stimulated the dissociation of Zn^<2+> form the protein. Chronic application of a Zn^<2+> chelator, dithizone, into rat hippocampus decreased the level of L-glutamate but not those of the other transmitters.2.Translocation of protein kinase C (PKC) : In hippocampla synaptoneurosome, NMDA and L-glutamate induced translocation of PKC from cytosol to plasma membrane. The NMDA-induced translocation was dependent on Ca^<2+> and required for trace amount of endogenous Zn^<2+>. The effect of NMDA showed a developmental changes, where the effect was most obvious at 7 day from the birth.3.Regulation of L-glutamate release: Zn^<2+> inhibited release of L-glutamate, but not those of GABA and acethycholine, from hippocampal slices, while dithizone increased the L-glutamate release.4.Inhibition of PI turnover: The inhibition of NMDA on carbachol-induced PI(phosphatidilinositol) turnover was suppressed by Zn^<2+> The effect was caused by inhibition of Ca^<2+> influx by Zn^<2+>.

1. L-谷氨酸对Zn^<2+>结合蛋白的影响：我们在大鼠海马的胞浆部分发现了一种Zn^<2+>结合蛋白。L-谷氨酸及其类似物刺激Zn^2+从蛋白质上解离。在大鼠海马内长期应用锌离子螯合剂双硫腙可降低L-谷氨酸的水平，但对其他递质的水平无影响。2.蛋白激酶C（PKC）的转位：在海马突触神经体中，NMDA和L-谷氨酸可诱导PKC从胞浆转位至质膜。NMDA诱导的易位依赖于Ca^<2+>和微量的内源性Zn^<2+>。L-谷氨酸释放的调节：Zn^2+抑制海马脑片L-谷氨酸的释放，但不抑制GABA和乙酰胆碱的释放，而双硫腙增加L-谷氨酸的释放。Zn^<2+>可抑制NMDA对卡巴胆碱诱导的PI（phosphatidilinositol）转换的抑制作用，其作用机制可能与Zn^<2 +>抑制Ca^<2 +>内流有关。

项目成果

Y.Koyama et al.: "L-Glutamate-induced swelling of cultured astrocytes is dependent on extracelluar Ca^<2+>" Neurosci.Lett.122. 210-212 (1991)

Y.Koyama 等人：“L-谷氨酸诱导的培养星形胶质细胞的肿胀依赖于细胞外Ca^2”Neurosci.Lett.122。

S.Etoh et al.: "NMDA induces protein kinase C translocation in hippocampal slices of immature rat brains" Neurosci. Lett.126. 119-122 (1991)

S.Etoh 等人：“NMDA 诱导未成熟大鼠大脑海马切片中的蛋白激酶 C 易位”Neurosci。

J.Kitanaka and A.Baba: "Cytochasin B inhibits phosphoinositide hydrolysis in rat hippocampal slices"

J.Kitanaka 和 A.Baba：“Cytochasin B 抑制大鼠海马切片中的磷酸肌醇水解”

Y.Koyama and A.Baba: "Different roles of Cl^- and Ca^<2+> influxes in Lーglutamateーinduced swelling of cultured astrocytes" in submitted.

Y.Koyama 和A.Baba：“Cl^- 和Ca^2+ 流入在L-谷氨酸诱导的培养星形胶质细胞肿胀中的不同作用”提交。

Baba et al.: "Inhibition of NMDA-induced protein kinase C trans-location by a Zn2+ chelator:Implication of intracellular Zn2+" Brain Res.557. 103-108 (1991)

Baba 等人：“Zn2 螯合剂对 NMDA 诱导的蛋白激酶 C 易位的抑制：细胞内 Zn2 的影响”Brain Res.557。