Bhave S V, Snell L D, Tabakoff B, Hoffman P L
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Alcohol Clin Exp Res. 1996 Aug;20(5):934-41. doi: 10.1111/j.1530-0277.1996.tb05274.x.
Ethanol is a potent inhibitor of the function of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in various neuronal preparations. In primary cultures of cerebellar granule cells, ethanol was suggested to interact with the glycine co-agonist site of the receptor by a mechanism involving protein kinase C. In the present study, the interaction of ethanol with various sites on the NMDA receptor was examined in primary cultures of cerebral cortical cells from embryonic rats. NMDA receptor function was determined by measuring increases in intracellular Ca2+ with fura-2 fluorescence. Ethanol inhibited the function of the NMDA receptor in cerebral cortical cells, but in contrast to the results in cerebellar granule cells, phorbol ester treatment did not inhibit the NMDA response, and ethanol did not alter the effect of glycine on NMDA receptor function. Ethanol also did not affect inhibition of the NMDA response by Mg2+ or dizocilpine. The results support the hypothesis that the mechanism of ethanol inhibition of NMDA receptor function can vary in neurons from different brain regions.
乙醇是多种神经元制剂中谷氨酸受体N-甲基-D-天冬氨酸（NMDA）亚型功能的强效抑制剂。在小脑颗粒细胞的原代培养中，乙醇被认为通过一种涉及蛋白激酶C的机制与受体的甘氨酸协同激动剂位点相互作用。在本研究中，在来自胚胎大鼠的大脑皮质细胞原代培养中检测了乙醇与NMDA受体上不同位点的相互作用。通过用fura-2荧光测量细胞内Ca2+的增加来确定NMDA受体功能。乙醇抑制大脑皮质细胞中NMDA受体的功能，但与小脑颗粒细胞中的结果相反，佛波酯处理并未抑制NMDA反应，并且乙醇未改变甘氨酸对NMDA受体功能的影响。乙醇也不影响Mg2+或地卓西平对NMDA反应的抑制作用。这些结果支持了这样的假说，即乙醇抑制NMDA受体功能的机制在不同脑区的神经元中可能有所不同。
