ETHANOL MODIFICATION OF NEUROTRANSMITTER RECEPTOR

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。这些变化可能 造成酒精的急性醉人效应，以及 受体功能的适应可能与酒精有关 耐受性和/或身体依赖性。这个 咪唑苯并二氮类，Ro15-4513，可能的乙醇拮抗剂， 用来评估GABA/苯二氮卓类受体的作用 在酒精的急性影响中。Ro15-4513降低了 不协调，但不是乙醇对小鼠的降温效应， 提示乙醇的某些作用可能涉及GABA 受体复合体。采用生化和行为学方法 确定受体偶联腺苷环化酶(AC)的作用 乙醇对系统的影响。在小鼠大脑皮层，Low 乙醇在体外刺激异丙肾上腺素的浓度- 敏感的AC活性和改变的高亲和力激动剂结合。 数据表明，乙醇会影响鸟嘌呤类物质Gs 核苷酸结合蛋白。在酒精耐受/依赖方面 动物，高亲和力激动剂的结合是检测不到的，并且 异丙肾上腺素等激动剂对AC活性的刺激作用 减少，让人联想到在异源 脱敏，这可能涉及G蛋白的变化 功能。对这些动物大脑皮质G蛋白的分析 霍乱毒素和百日咳毒素诱导的32P-ADP核糖基化 而SDS-PAGE显示Gs的数量选择性减少。 腺苷酸环化酶活性在人体内的潜在重要性 这一发现表明，对酒精的神经适应 服用能刺激大脑AC活动的Forsklin， 克服了中国对宽容发展的封锁 去甲肾上腺素耗竭。慢性酒精摄取产生 大鼠β肾上腺素能受体特性的不同变化 小脑(主要是β-2受体)比皮质和 海马体(主要是β-1)，表明乙醇影响 这些受体亚型和/或区域G蛋白的偶联 特征，以选择性的方式。慢性酒精摄入 也选择性地减少了Mu阿片受体的数量 大脑皮层。

Ethanol selectively alters the function of neurotransmitter and neuromodulator receptors in the CNS. These changes may contribute to the acute, intoxicating effects of ethanol, and adaptations in receptor function may be associated with ethanol tolerance and/or physical dependence. The imidazobenzodiazepine, Ro15-4513, a putative ethanol antagonist, was used to assess the role of the GABA/benzodiazepine receptor in the acute effects of ethanol. Ro15-4513 reduced the incoordinating, but not the hypothermic effect of ethanol in mice, indicating the certain of ethanol's actions may involve the GABA receptor complex. Biochemical and behavioral methods were used to determine the role of receptor-coupled adenylate cyclase (AC) systems in ethanol's effects. In mouse cerebral cortex, low concentrations of ethanol in vitro stimulated isoproterenol- sensitive AC activity and altered high-affinity agonist binding. The data suggested that ethanol affected Gs, the guanine nucleotide binding protein. In ethanol tolerant/dependent animals, high-affinity agonist binding was undetectable, and stimulation of AC activity by isoproterenol and other agonists was reduced, reminiscent of changes that occur during heterologous desensitization, and that may involve a change in G-protein function. Analysis of cortical G-proteins in these animals by cholera toxin and pertussis toxin-induced 32P-ADP ribosylation and SDS-PAGE revealed a selective decrease in the amount of Gs. The potential importance of adenylate cyclase activity in neuroadaptation to ethanol was suggested by the finding that administration of forskolin, which stimulates brain AC activity, overcame the blockade of tolerance development produced by norepinephrine depletion. Chronic ethanol ingestion produced different changes in beta-adrenergic receptor characteristics in cerebellum (primarily beta-2 receptors) than in cortex and hippocampus (primarily beta-1), suggesting that ethanol affects the coupling of these receptor subtypes, and/or regional G-protein characteristics, in a selective manner. Chronic ethanol ingestion also selectively reduced the number of mu opiate receptors in cerebral cortex.