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Functional relationship between NMDA-induced neuronal injury and various neurotransmitter receptors

NMDA诱导的神经元损伤与各种神经递质受体的功能关系

基本信息

批准号：
04670127
负责人：
OHKUMA Seitaro
金额：
$ 1.34万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670127/
关键词：
NMDA receptor neuronal death GABA_A receptor ca-channel blocker NG108-15 cells Ca influx [^3H]MK-801 binding cerebral cortical neurons NG108-15

项目摘要

In the present study, effect of various neurotransmitter receptors on NMDA-induced neuronal injury was investigated using primary cultured cerebral cortical neurons and whether neuroblastoma x glioma hybrid NG108-15 (NG cells) possess NMDA receptor was also examined. The follwing results were obtained.1) NG cells showed the response of calcium influx to NMDA receptor stimulation and had the binding sites of [^3H]MK-801, a radiolabeled ligand specific for NMDA receptor, which assumed to be similar to those found in neurons in rodents brain. These results indicate that NG cells possess NMDA receptor with pharmacological property.2) NMDA dose-dependently induced the leakage of LDH activity from cerebral cortical neurons during 1 hr subsequent to the exposure to NMDA for 15 min. This NMDA-induced leakage of LDH activity was significantly inhibited by GABA_A receptor stimulation, while the stimulation of muscarinic and beta-receptors showed no effects on NMDA-induced leakage of LDH activity.3)NMDA induced [^<45>Ca]influx into cerebral cortical neurons. Several GABA_A receptor agonists enhanced this NMDA-induced [^<45>Ca]influx. Chloride channel inhibitors functionally coupling to GABA_A receptor such as picrotoxinin and TBPS showed no inhibition, while voltage-dependent calcium channel blockers reduced this stimulatory effects of GABA_A receptor agonists.

在本研究中，各种神经递质受体对NMDA诱导的神经元损伤的影响进行了研究，使用原代培养的大脑皮层神经元和神经母细胞瘤x胶质瘤杂交NG 108 -15（NG细胞）是否具有NMDA受体也进行了检查。结果表明：1）NG细胞对NMDA受体刺激有钙内流反应，并具有NMDA受体特异性配体[^3H]MK-801的结合位点，推测其与啮齿类动物脑神经元的结合位点相似。2）NMDA剂量依赖性地诱导NMDA作用15 min后1 h内大脑皮层神经元LDH活性的漏出，GABA_A受体可明显抑制NMDA诱导的LDH活性的漏出。而M受体和β受体的刺激对NMDA诱导的LDH活性泄漏没有影响。3）NMDA诱导<45>的大脑皮层神经元内流。几种GABA_A受体激动剂增强NMDA诱导的[^<45>Ca]内流。与GABA_A受体功能性偶联的氯离子通道抑制剂如印防己毒素和TBPS没有抑制作用，而电压依赖性钙通道阻断剂则减弱GABA_A受体激动剂的这种刺激作用。