ETHANOL MODIFICATION OF NEUROTRANSMITTER RECEPTOR-EFFECTOR COUPLING PROCESSES

乙醇对几种神经递质受体效应器的影响 偶联系统进行了研究，以阐明特异性 乙醇的作用、乙醇作用的部位和机制以及 这些系统在适应气候变化的慢性影响方面可能发挥的作用 乙醇（即，耐受性和/或身体依赖性）。 大脑皮质 在C57 B1小鼠中，乙醇增加了β-肾上腺素能神经元的活性， 受体偶联腺苷酸环化酶（AC）的剂量依赖性方式。 乙醇作用的特异性位点为：β-肾上腺素能受体N（s） (the鸟嘌呤核苷酸结合蛋白）和AC的催化单元。 乙醇也促进了鸟嘌呤核苷酸负载N（s）的相互作用 在AC 初步结果表明，在耐乙醇和 依赖性小鼠以及大鼠中，鸟嘌呤刺激皮质AC 核苷酸和异丙肾上腺素（ISO）减少，表明适应性 在生化水平上的反应。 类似的结果（即，减少 对鸟嘌呤核苷酸和ISO刺激的敏感性）被发现， 大鼠松果体AC，表明对这一点的普遍影响 受体效应系统 相比之下，乙醇，急性或慢性， 没有改变小鼠纹状体中阿片类药物对AC的抑制。 的影响 乙醇似乎对使用N（s）的系统相对特异， 到N（i）。 乙醇也影响受体与另一种生化物质的偶联 传感器，磷脂酰肌醇（PI）周转。 乙醇抑制了这一点 活性，并且在用乙醇对小鼠进行长期体内治疗后， 增加PI周转对胆碱能刺激的敏感性 激动剂，但不是去甲肾上腺素能激动剂。 这些变化， 先前观察到的配体结合的改变，证明了 乙醇诱导的受体数量改变的功能相关性 CNS。 这种变化可能与乙醇的特定症状有关 戒断 总的来说，研究表明乙醇具有特定的位点， 在中枢神经系统的作用，适应发生在这些网站后， 用乙醇长期治疗动物，导致耐受性， 身体依赖。

The effects of ethanol on several neurotransmitter receptor-effector coupling systems were investigated in order to elucidate the specificity of ethanol's effects, the site(s) and mechanisms of ethanol action, and the possible role of these systems in adaptation to the chronic effects of ethanol (i.e., tolerance and/or physical dependence). In cerebral cortex of C57B1 mice, ethanol increased the activity of beta-adrenergic receptor-coupled adenylate cyclase (AC) in a dose-dependent manner. Specific sites of ethanol action were: the beta-adrenergic receptor N(s) (the guanine nucleotide-binding protein) and the catalytic unit of AC. Ethanol also promoted the interaction of guanine nucleotide-loaded N(s) with AC. Preliminary results showed that in ethanol-tolerant and -dependent mice, as well as in rats, stimulation of cortical AC by guanine nucleotides and isoproterenol (ISO) was reduced, suggesting an adaptive response at the biochemical level. Similar results (i.e., reduced sensitivity to stimulation by guanine nucleotides and ISO) were found for rat pineal gland AC, indicating a generalized effect on this receptor-effector system. In contrast, ethanol, acutely or chronically, did not alter opiate inhibition of AC in mouse striatum. The effect of ethanol seems to be relatively specific for systems using N(s), as opposed to N(i). Ethanol also affected receptor coupling to another biochemical transducer, phosphatidylinositol (PI) turnover. Ethanol inhibited this activity and, after chronic in vivo treatment of mice with ethanol, there was increased sensitivity of PI turnover to stimulation by cholinergic agonist, but not by a noradrenergic agonist. These changes paralleled previously observed alterations in ligand binding, demonstrating a functional correlate of ethanol-induced alterations in receptor number in the CNS. This change may be associated with specific symptoms of ethanol withdrawal. Overall, the studies illustrate the ethanol has specific sites of action in the CNS, and that adaptation occurs at these sites after chronic treatment of animals with ethanol, which results in tolerance and physical dependence.