ETHANOL INHIBITS NMDA RECEPTOR-MEDIATED EXCITOTOXICITY IN RAT PRIMARY NEURONAL CULTURES

被引:105
作者
CHANDLER, LJ [1 ]
SUMNERS, C [1 ]
CREWS, FT [1 ]
机构
[1] UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32611
关键词
ETHANOL; NMDA RECEPTORS; NEUROTOXICITY; EXCITOTOXICITY; GLUTAMATE;
D O I
10.1111/j.1530-0277.1993.tb00726.x
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Excessive or prolonged stimulation of N-methyl-D-aspartate (NMDA) receptors appears to play an important role in many neurodegenerative processes in brain through a process known as excitotoxicity. This study examined the effects of ethanol on NMDA receptor-mediated excitotoxicity in primary neuronal cultures obtained from embryonic rat whole brain. Neurotoxicity was quantitated by measuring the amount of lactate dehydrogenase released into the media during a 20-hr time period following NMDA washout. Exposure of 12-to 14-day-old cultures to NMDA in Mg2+-free HEPES buff er (pH 7.4) for a 25-min period resulted in a concentration-dependent toxicity (EC50 = 54 mum). Time-course experiments showed that exposure to NMDA for as little as 5 min was excitotoxic and reached a plateau after a 20-min exposure period. Preincubation of the cultures with ethanol (25 to 200 mm) resulted in a concentration-dependent inhibition of NMDA-mediated toxicity with approximately 38% inhibition produced by 25 mm ethanol and essentially complete inhibition at 200 mm ethanol (IC50 = 60 mm). Increasing the glycine concentration to 100 mum did not potentiate NMDA neurotoxicity or antagonize the neuroprotective eff ect of ethanol. NMDA-Mediated excitotoxicity was reduced by approximately 50% by the glycine antagonist 7-chloro-kynurenate (50 mum). Ethanol (50 mm) reduced NMDA neurotoxicity similar to 7-chlorokynurenate, and the two together produced greater inhibition than either alone. These results show that intoxicating concentrations of ethanol can potently inhibit NMDA receptor-mediated excitotoxicity and may have important implications in terms of ethanols interactions with brain trauma, ischemia, and other neuropathologies associated with NMDA receptor-mediated neurotoxicity.
引用
收藏
页码:54 / 60
页数:7
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