Valverius P, Borg S, Valverius M R, Hoffman P L, Tabakoff B
Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
Exp Neurol. 1989 Sep;105(3):280-6. doi: 10.1016/0014-4886(89)90131-3.
The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral cortical and cerebellar membrane preparations was not different in alcoholics compared to that in controls, suggesting that the number of beta-adrenergic receptors was not affected by chronic ethanol ingestion. Agonist binding data, however, indicated the loss of the high-affinity agonist binding state of the beta-adrenergic receptor, representing the receptor-guanine nucleotide binding protein (Gs) complex. Such changes were observed in cerebral cortex but not in cerebellum of intoxicated alcoholics. These data suggest that cerebral cortical beta-adrenergic receptors are uncoupled from adenylate cyclase in these subjects. In cerebral cortical and cerebellar membranes of sober alcoholics both the high- and low-affinity agonist binding sites were observed. These findings are similar to those seen in animal studies and suggest that the effect of chronic ethanol ingestion on beta-adrenergic receptor-adenylate cyclase coupling is brain region specific and reversible with abstinence. Ethanol-induced changes in the coupling of receptors to adenylate cyclase may contribute to the physiological and behavioral manifestations of alcohol abuse.
测定了非酒精对照组、配对的醉酒和清醒酗酒者死后获得的脑组织中激动剂和拮抗剂与β-肾上腺素能受体的结合情况，以评估受体的状态及其与腺苷酸环化酶的偶联。与对照组相比，酗酒者大脑皮质和小脑膜制剂中拮抗剂碘氰吲哚洛尔的结合没有差异，这表明慢性乙醇摄入不影响β-肾上腺素能受体的数量。然而，激动剂结合数据表明，β-肾上腺素能受体高亲和力激动剂结合状态丧失，该状态代表受体-鸟嘌呤核苷酸结合蛋白（Gs）复合物。在醉酒酗酒者的大脑皮质中观察到了这种变化，但在小脑中未观察到。这些数据表明，在这些受试者中，大脑皮质β-肾上腺素能受体与腺苷酸环化酶解偶联。在清醒酗酒者的大脑皮质和小脑膜中，均观察到了高亲和力和低亲和力激动剂结合位点。这些发现与动物研究中的发现相似，表明慢性乙醇摄入对β-肾上腺素能受体-腺苷酸环化酶偶联的影响具有脑区特异性，且戒酒后可逆转。乙醇诱导的受体与腺苷酸环化酶偶联的变化可能导致酒精滥用的生理和行为表现。
