REQUIREMENT FOR GLYCINE IN ACTIVATION OF NMDA-RECEPTORS EXPRESSED IN XENOPUS OOCYTES
REQUIREMENT FOR GLYCINE IN ACTIVATION OF NMDA-RECEPTORS EXPRESSED IN XENOPUS OOCYTES
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DOI：
10.1126/science.2841759
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发表时间：
1988-08-12
期刊：
影响因子：
56.9
通讯作者：
DINGLEDINE, R
中科院分区：
文献类型：
--
作者：
KLECKNER, NW;DINGLEDINE, R
N-甲基-D-天冬氨酸（NMDA）受体参与脑内许多可塑性和病理过程。已报道甘氨酸可增强神经元和注射大鼠脑信使RNA的异种卵母细胞的NMDA反应。甘氨酸是激活卵母细胞中NMDA受体所必需的。在电压钳位的卵母细胞，灌注或快速压力应用NMDA到信使RNA注射的卵母细胞引起了一个独特的离子电流没有添加甘氨酸。然而，当加入甘氨酸时，NMDA诱发了大的内向电流。产生半最大反应所需的甘氨酸浓度为670纳摩尔，在不存在甘氨酸的情况下，甘氨酸剂量-反应曲线外推至零。甘氨酸的几种类似物可以替代甘氨酸，其中D-丝氨酸和D-丙氨酸是最有效的。D-氨基酸有效的观察结果对于开发靶向甘氨酸位点的药物非常重要。
Receptors forN-methyl-D-aspartate (NMDA) are involved in many plastic and pathological processes in the brain. Glycine has been reported to potentiate NMDA responses in neurons and inXenopusoocytes injected with rat brain messenger RNA. Glycine is now shown to be absolutely required for activation of NMDA receptors in oocytes. In voltage-clamped oocytes, neither perfusion nor rapid pressure application of NMDA onto messenger RNA-injected oocytes caused a distinct ionic current without added glycine. When glycine was added, however, NMDA evoked large inward currents. The concentration of glycine required to produce a half-maximal response was 670 nanomolar, and the glycine dose-response curve extrapolated to zero in the absence of glycine. Several analogs of glycine could substitute for glycine, among which D-serine and D-alanine were the most effective. The observation that D-amino acids are effective will be important in developing drugs targeted at the glycine site.