ALCOHOL AND THE HUMAN LEUKOCYTE BETA-RECEPTOR

最近人们认识到， 去甲肾上腺素敏感腺苷酸环化酶系统可能与 各种精神疾病。 肾上腺素能受体的改变是 被认为与药物和酒精中毒的发病机制有关 和撤退。 一种估计受体功能的方法， 大脑和其他器官是通过使用外围模型。 的情况 人白细胞β-肾上腺素能受体功能的变化 受体出现平行的变化，发生在β受体的 其他器官系统，包括心脏和大脑。 戒断综合征是指慢性酒精中毒或 镇静催眠药物的使用特点是一组生理学上的 肾上腺素能活动增加的体征和症状。 据推测 β受体功能的改变发生在人类身上， 这些生理效应。 我的实验室一直在研究 β-肾上腺素能受体在酒精急性反应中的作用 酒精戒断综合征的发病机制。 β受体 通过测量放射性配体与受体的结合来评估受体功能。 白细胞膜和β-激动剂刺激的环AMP的测量 在完整的白细胞中形成。 乙醇，在体外，被发现 引起异丙肾上腺素剂量增加， 在人类淋巴细胞中，洋地黄素刺激环AMp的产生。 这 这项研究将通过进一步研究其他因素的影响来扩展这些发现。 酒精、美沙酮、镇静催眠药物暴露对白细胞的影响 β-肾上腺素能受体，在体外。 此外，β-肾上腺素能受体 功能将随着时间的推移，在人类接受酒精，美沙酮 或镇静催眠药物戒断，并与血浆 去甲肾上腺素水平和受试者的临床状态 通过这项工作，我们希望研究酒精的潜在机制， 相关的药物滥用和停药， 神经递质受体水平与临床体征和症状 在病人身上。

It has recently been recognized that modifications in the activity of the noradrenergic sensitive adenylate cyclase system may be associated with a variety of psychiatric illnesses. Alterations in adrenergic receptors are thought to be involved in the pathogenesis of drug and alcohol intoxication and withdrawal. One method of estimating the function of receptors in brain and other organs is by use of peripheral models. In the case of the human leukocyte beta-adrenergic receptor, changes in the function of this receptor appear to parallel changes which occur in the beta-receptors of other organ systems, including heart and brain. The withdrawal syndrome which follows cessation of chronic alcohol or sedative-hypnotic drug use is characterized by a cluster of physiological signs and symptoms of increased adrenergic activity. It is hypothesized that modifications in beta-receptor function occur in man, which account for these physiological effects. My laboratory has been investigating the role of beta-adrenergic receptors in the acute response to alcohol and in the pathogenesis of the alcohol withdrawal syndrome. Beta-adrenergic receptor function is assessed by measurement of radioligand binding to leukocyte membranes and measurement of beta-agonist stimulated cyclic AMP formation in intact leukocytes. Ethyl alcohol, in vitro, was found to cause a dose department increase in isoproterenol- and prostaglandin-stimulated cyclic AMp production in human lymphocytes. This study will extend those findings by further examining the effect of other alcohols, methadone, sedative-hypnotic drug exposure on the leukocyte beta-adrenergic receptor, in vitro. In addition, beta-adrenergic receptor function will be followed over time in human undergoing alcohol, methadone or sedative-hypnotic drug withdrawal, and correlated with plasma norepinephrine levels, and the subjects' clinical state. Through this work we hope to examine the mechanism underlying alcohol and related drug intoxification and withdrawal, correlating changes at the level of a neurotransmitter receptor with clinical signs and symptoms seen in patients.