Navamani M, Morgan M, Williams R J
Division of Biochemistry and Molecular Biology, UMDS, Guy's Medical School, London, UK.
Eur J Pharmacol. 1997 Dec 4;340(1):27-34. doi: 10.1016/s0014-2999(97)01396-4.
Glutamate-evokes a Ca2+-dependent release of arachidonic acid from cultured neurones via the activation of NMDA and AMPA receptors. In this study we investigated whether exposing cultured striatal neurones either acutely or chronically to ethanol would modify these responses. Acute ethanol (100 mM, 15 min) inhibited the liberation of arachidonic acid evoked by a maximally effective concentration of glutamate, an affect which appeared to be mediated primarily by a reduction in NMDA receptor responsiveness. In contrast, chronic ethanol exposure caused a dose-dependent increase in the glutamate, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) evoked release of arachidonic acid, although ethanol was less potent at the AMPA response. Basal responses were not altered by acute or chronic ethanol and the concentrations of ethanol employed were not toxic. Chronic ethanol (100 mM, 48 h) increased NMDA-mediated neuronal damage at sub-maximal concentrations of the agonist, suggesting that an enhanced mobilisation of arachidonic acid may underly the potentiated excitotoxic neuronal loss observed following exposure to ethanol.
谷氨酸盐通过激活N-甲基-D-天冬氨酸（NMDA）受体和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体，引发培养神经元中花生四烯酸的钙离子依赖性释放。在本研究中，我们调查了急性或慢性暴露于乙醇是否会改变培养的纹状体神经元的这些反应。急性乙醇（100 mM，15分钟）抑制了由最大有效浓度的谷氨酸盐诱发的花生四烯酸释放，这种作用似乎主要是由NMDA受体反应性降低介导的。相比之下，慢性乙醇暴露导致谷氨酸盐、N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）诱发的花生四烯酸释放呈剂量依赖性增加，尽管乙醇对AMPA反应的作用较小。急性或慢性乙醇均未改变基础反应，所用乙醇浓度也无毒。慢性乙醇（100 mM，48小时）在次最大浓度的激动剂作用下增加了NMDA介导的神经元损伤，这表明花生四烯酸动员增强可能是乙醇暴露后观察到的增强的兴奋性毒性神经元损失的基础。
