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。 这些变化可能有助于 酒精的急性中毒作用，以及 受体功能可能与乙醇耐受性和/或 身体依赖。 先前的研究表明， 大脑皮质腺苷酸环化酶（AC）活性的β- 肾上腺素能激动剂和鸟嘌呤核苷酸，并减少高- 亲和力β-肾上腺素能激动剂结合，在大脑皮层中， 小鼠长期喂食乙醇。 数据显示， Gs的性质，刺激性鸟嘌呤核苷酸结合 蛋白质，在这些老鼠身上。 这一假设得到了一个 大脑皮层AC刺激减少的证明 通过乙醇喂养小鼠中的Gs起作用的其他药剂的活性， 与对照组相比，霍乱毒素的可用性降低- 催化的ADP-核糖基化的蛋白质迁移一样，在SDS- 聚丙烯酰胺凝胶 相比之下， 在百日咳毒素催化的ADP- 大脑皮质蛋白的核糖基化，或者在最初的研究中， 在通过蛋白质印迹法测量的Go-α或Gi-α的量中 分析. 因此，慢性乙醇摄入似乎选择性地 影响一个类似G家族中的一个的数量和/或功能 proteins. 乙醇对受体-AC耦合的影响是脑 具体区域。 β-肾上腺素能激动剂刺激的AC的变化 活性和高亲和力激动剂结合相似， 与对照组相比， 小脑则无明显变化。 这一区域 特异性得到了放射自显影分析的支持， 毛喉素结合的亲和力，这被认为反映了结合 Gs-alpha-AC复合物 区域的特殊性 乙醇对受体-效应器偶联的影响可能有助于 对慢性酒精摄入的特定行为反应。

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. Previous work showed decreased stimulation of cerebral cortical adenylate cyclase (AC) activity by beta- adrenergic agonists and guanine nucleotides, and decreased high- affinity beta-adrenergic agonist binding, in cerebral cortex of mice fed ethanol chronically. The data suggested an alteration in the properties of Gs, the stimulatory guanine nucleotide binding protein, in these mice. This hypothesis was supported by a demonstration of reduced stimulation of cerebral cortical AC activity by other agents that act through Gs in ethanol-fed mice, compared to controls, and reduced availability for cholera toxin- catalyzed ADP-ribosylation of a protein migrating like Gs on SDS- polyacrylamide gels. In contrast, there was no difference between control and ethanol-fed mice in pertussis toxin-catalyzed ADP- ribosylation of cerebral cortical proteins or, in initial studies, in the quantity of Go-alpha or Gi-alpha measured by Western blot analysis. Chronic ethanol ingestion thus appears to selectively affect the amount and/or function of one of a family of similar G proteins. The effects of ethanol on receptor-AC coupling are brain region-specific. Changes in beta-adrenergic agonist-stimulated AC activity and high-affinity agonist binding were similar in hippocampus and cortex of ethanol-fed mice, compared to controls, while little change was observed in cerebellum. This regional specificity was supported by autoradiographic analysis of high- affinity forskolin binding, which is believed to reflect binding to the Gs-alpha-AC complex. The regional specificity of the effects of ethanol on receptor-effector coupling may contribute to specific behavioral responses to chronic ethanol ingestion.