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

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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.