ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

据推测，乙醇在中枢神经系统中的作用 是因为它有能力扰乱神经元的结构 膜脂。膜结合酶的活性， 其由周围脂类的性质调制，可以 用作定位乙醇的特定作用部位的探针 在神经细胞膜内。(Na+，K+)ATPase存在于两个 在大脑中形成，对哇巴因有高亲和力和低亲和力。快感-- 亲和力成分被认为定位于神经元 膜。高浓度乙醇，在体外，选择性地 抑制该酶的活性并增加哇巴因敏感性 这种酶的高亲和力形式。在长期体内摄取后 乙醇，产生耐受性和身体依赖， 这种酶的神经元形式对哇巴因的敏感性是 选择性增加，这种形式的酶是抗药性的 乙醇的体外效应。单胺氧化酶(MAO) 大脑也以两种形式存在，A和B，我们之前已经展示过 乙醇选择性地抑制MAO的B型，这也是 在血小板中发现。我们发现对血小板MAO的抑制 与酗酒者相比，酗酒者的血小板中的乙醇含量增加 控制。然而，血小板腺苷环化酶的活性是 酗酒者的血小板较低。这两项活动可能是 作为饮酒的标志很有用。乙醇对人体的影响 在体内对神经递质代谢的其他酶有 正在研究中。使用一种不可逆的DOPA抑制剂 脱羧酶，单氟甲基多巴，我们发现 儿茶酚胺在几个脑区和外周的代谢 长期摄入酒精后，器官会增加。提纯 大脑中的酶。琥珀酸半醛还原酶， 可能参与了GABA的新陈代谢，现已启动。这些 研究增加了我们对神经元调节的理解 活动，如神经递质周转反映的，和 乙醇对这种活性的影响。

It has been hypothesized that the actions of ethanol in the CNS result from its ability to perturb the structure of neuronal membrane lipids. The activities of membrane-bound enzymes, which are modulated by the properties of surrounding lipids, may serve as probes to localize specific sites of action of ethanol within the neuronal membrane. (Na+, K+)ATPase exists in two forms in brain, with high and low affinity for ouabain. The high- affinity component is thought to be localized in neuronal membranes. High concentrations of ethanol, in vitro, selectively inhibited the activity and increased ouabain sensitivity of the high-affinity form of the enzyme. After chronic, in vivo ingestion of ethanol, producing tolerance and physical dependence, the sensitivity to ouabain of the neuronal form of the enzyme was selectively increased, and this form of the enzyme was resistant to the in vitro effect of ethanol. Monoamine oxidase (MAO) in brain also exists in two forms, A and B, and we previously showed that ethanol selectively inhibits the B form of MAO, which is also found in platelets. We have found that inhibition of platelet MAO by ethanol is increased in platelets of a alcoholics compared to controls. The activity of platelet adenylate cyclase, however, is lower in platelets of alcoholics. These two activities may be useful as markers for alcohol consumption. The effects of ethanol in vivo on other enzymes of neurotransmitter metabolism are being studied. Using an irreversible inhibitor of DOPA decarboxylase, monofluoromethyldopa, we have found that catecholamine metabolism in several brain areas and in periperhal organs is increased after chronic ethanol ingestion. Purification of the brain enzyme. Succinic semialdehyde reductase, which may be involved in GABA metabolism, has been initiated. These studies add to our understanding of the regulation of neuronal activity, as reflected by neurotransmitter turnover, and the effects of ethanol on that activity.