ETHANOL MODIFICATION OF NEUROTRANSMITTER RECEPTOR-EFFECTOR COUPLING

乙醇选择性地改变神经递质的功能， 中枢神经系统中的神经调质受体，以及受体功能的适应 可能与乙醇耐受性和/或身体依赖性有关。 以前的工作表明，不同的腺苷酸环化酶的刺激减少， 激动剂和鸟嘌呤核苷酸，并降低高亲和力结合， β-肾上腺素能激动剂和毛喉素在小鼠某些脑区 长期喂食乙醇。这些结果表明， 刺激性鸟嘌呤核苷酸结合蛋白质的质的变化， GS.两种（46和52 kDa）形式的Gs-α和Gi-α的定量 然而，通过蛋白质印迹分析， 在乙醇喂养的小鼠中这些蛋白质的水平没有显著变化， Gs-alpha mRNA的原位杂交研究也显示无变化。 两种形式的Gs-alpha在脑区中的比例差异 发现46 kDa的形式对霍乱有抗性 毒素催化的ADP-核糖基化。数据表明慢性乙醇 摄入可能会改变Gs-alpha的性质，而不是数量， 进一步表征两种形式的蛋白质在 乙醇喂养的小鼠是有必要的。NMDA受体系统也发生了变化， 乙醇喂养的小鼠。通过膜结合和放射自显影测量 MK-801是一种NMDA受体的非竞争性拮抗剂， 受体在海马和其他脑区上调， 乙醇喂养的小鼠。约束力变化的时间过程 酒精戒断癫痫的易感性此外， 乙醇戒断性癫痫（WSP）患者海马区MK-801 结合位点比小鼠培育的耐酒精戒断癫痫发作 (WSR)在慢性乙醇摄入之前和之后。这些发现 支持NMDA受体门控通道在乙醇戒断中的作用。 在初步研究中，士的宁不敏感的甘氨酸结合不是 增加乙醇喂养的小鼠，表明NMDA的功能的变化， 受体门控通道，而不是增加数量的受体通道 配合物

Ethanol selectively alters the function of neurotransmitter and neuromodulator receptors in the CNS, and adaptations in receptor function may be associated with ethanol tolerance and/or physical dependence. Previous work showed decreased stimulation of adenylate cyclase by various agonists and by guanine nucleotides, and decreased high-affinity binding of a beta-adrenergic agonist and forskolin in certain brain regions of mice fed ethanol chronically. These results suggested a quantitative or qualitative change in the stimulatory guanine nucleotide binding protein, Gs. Quantitation of the two (46 and 52 kDa) forms of Gs-alpha, and of Gi-- alpha, in various brain regions by Western blot analysis, however, revealed no significant change in the levels of these proteins in ethanol-fed mice, and in situ hybridization studies of Gs-alpha mRNA also showed no change. Differences in proportion of the two forms of Gs-alpha among brain regions were observed, and the 46 kDa form was found to be resistant to cholera toxin-catalyzed ADP-ribosylation. The data indicate that chronic ethanol ingestion may alter the properties rather than amount of Gs-alpha, and further characterization of the function of the two forms of the protein in ethanol-fed mice is warranted. The NMDA receptor system is also changed in ethanol-fed mice. As measured by membrane binding and autoradiographic studies of MK-801, a non-competitive antagonist at the NMDA receptor, this receptor is up-regulated in hippocampus and other brain areas of ethanol-fed mice. The time course of changes in binding parallels susceptibility to ethanol withdrawal seizures. In addition, mice bred to be prone to ethanol withdrawal seizures (WSP) have more hippocampal MK-801 binding sites than mice bred to be resistant to ethanol withdrawal seizures (WSR), both before and after chronic ethanol ingestion. These findings support a role for the NMDA receptor-gated channel in ethanol withdrawal. In preliminary studies, strychnine-insensitive glycine binding was not increased in ethanol-fed mice, suggesting a change in the function of NMDA receptor-gated channels rather than an increased number of receptor-channel complexes.