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节剂受体与受体的适应性 功能可能与酒精耐受性和/或生理 依赖。先前的研究表明腺苷的刺激减少 由各种激动剂和鸟嘌呤核苷酸引起的环化酶，并减少 β-肾上腺素能激动剂与Forsklin在CER中的高亲和力结合 长期饮用乙醇的小鼠的大脑区域。这些结果 指刺激性的量或质的变化 鸟嘌呤核苷酸结合蛋白，Gs。两者的量化(46和 52 kDa)形式的Gs-α，以及其他几种G-蛋白α和β 然而，通过蛋白质印迹分析，不同大脑区域中的亚基， 显示这些蛋白质的水平没有显著变化 酒精喂养的小鼠。两种类型Gs-α的比例差异 在脑区之间进行了观察，发现46 kDa的形式是 抵抗霍乱毒素催化的ADP-核糖基化。数据表明 长期摄入乙醇可能会改变这些特性，而不是 Gs-α的量，并进一步刻画了 酒精喂养的小鼠体内存在两种形式的蛋白质是有根据的。NMDA 酒精喂养的小鼠的受体系统也发生了变化。根据mem的测量- 非竞争性药物MK-801的膜结合和放射自显影研究 作为NMDA受体的拮抗剂，这种受体在 酒精喂养的小鼠的海马区和其他脑区。时间进程 对酒精戒断敏感性的结合类似物的变化 癫痫发作。此外，培育出容易戒断酒精的小鼠 癫痫(WSP)小鼠海马区MK-801结合位点数较多 对酒精戒断发作(WSR)具有抵抗力，之前和 在长期摄入酒精后。这些发现支持了 酒精戒断中的NMDA受体门控通道。在预赛中 研究表明，在乙醇中，对NMDA敏感的谷氨酸结合也会增加。 喂小鼠，而士的宁不敏感的甘氨酸结合不是， 提示NMDA受体门控的功能结构发生了变化 频道。

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 cer- tain 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 several other G-protein alpha and beta subunits, in various brain regions by Western blot analysis, however, revealed no significant change in the levels of these proteins in ethanol-fed mice. 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 mem- brane 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, NMDA-sensitive glutamate binding was also increased in ethanol- fed mice, while strychnine-insensitive glycine binding was not, suggesting a change in the structure of function of NMDA receptor-gated channels.