Valverius P, Hoffman P L, Tabakoff B
Mol Pharmacol. 1987 Aug;32(1):217-22.
Low concentrations of ethanol (10-100 mM), added to assays in vitro, altered agonist (isoproterenol) binding to mouse cerebral cortical beta-adrenergic receptors in a reversible manner. Ethanol decreased the affinity of the high affinity form of the receptor for isoproterenol but had no effect on the affinity of the low affinity form of the receptor, the proportion of high and low affinity forms of the receptor, the total number of agonist-binding sites, or antagonist binding. The selective effect of ethanol on the properties of the high affinity agonist-binding site suggested that ethanol alters the characteristics of the complex of the receptor and Gs, the guanine nucleotide-binding protein. In cerebral cortical membranes of mice that had ingested ethanol chronically, isoproterenol binding data were best fit by a one-site model, even in the absence of guanine nucleotides. This change, when considered together with previously reported changes in adenylate cyclase activity, is reminiscent of heterologous desensitization of the beta-adrenergic receptor. Thus, both acute and chronic ethanol administration may produce changes in adrenergic function in brain.
在体外实验中添加低浓度乙醇（10 - 100 mM），会以可逆方式改变激动剂（异丙肾上腺素）与小鼠大脑皮质β - 肾上腺素能受体的结合。乙醇降低了受体高亲和力形式对异丙肾上腺素的亲和力，但对受体低亲和力形式的亲和力、受体高亲和力和低亲和力形式的比例、激动剂结合位点总数或拮抗剂结合均无影响。乙醇对高亲和力激动剂结合位点特性的选择性作用表明，乙醇改变了受体与鸟嘌呤核苷酸结合蛋白Gs复合物的特性。在长期摄入乙醇的小鼠大脑皮质膜中，即使在没有鸟嘌呤核苷酸的情况下，异丙肾上腺素结合数据也最适合用单点模型来拟合。当将这一变化与先前报道的腺苷酸环化酶活性变化一起考虑时，这让人联想到β - 肾上腺素能受体的异源脱敏。因此，急性和慢性乙醇给药都可能导致大脑中肾上腺素能功能的变化。
