ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

据推测，乙醇在中枢神经系统中的作用是由于 其扰乱神经元膜脂质结构的能力。 的 活性的膜结合酶，这是调制的性质 可以作为探针定位特定的位点， 乙醇在神经元膜内的作用。 (Na~（+，K ~+）ATP酶存在于 脑中有两种形式，对哇巴因有高亲和力和低亲和力。 的 高亲和力组分被认为定位于神经元膜中。 乙醇在体外选择性地影响活性和哇巴因敏感性 酶的高亲和力形式。 类似地，在体内， 摄入乙醇，产生耐受性和身体依赖性，只有 神经元酶的性质被改变。 因为只有高 乙醇浓度影响体外酶活性，我们发现没有 去甲肾上腺素增强乙醇抑制作用，酶的作用 抑制乙醇在CNS中的作用仍然是开放的。 但 酶活性的选择性变化揭示了膜脂的改变 微区可能与乙醇的适应性反应有关。 单胺氧化酶（MAO）也以两种形式存在，A和B。 乙醇 选择性抑制人血小板和脑中的B型MAO 膜，通过脂质的扰动。 在C57 B1小鼠的大脑中， 避免酒精的DBA小鼠，乙醇注射导致水平增加 苯乙胺（PEA），MAO-B的底物，可能参与 加固. 因此，对MAO活性的抑制可能在细胞凋亡中起作用。 乙醇的生理作用，除了证明 乙醇在中枢神经系统中的生化作用的特异性。 这个项目 还包括神经胶质调节神经递质天冬氨酸的研究 代谢，增加了我们对调节机制的理解， 神经元活动

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. Ethanol, in vitro, selectively affects the activity and ouabain sensitivity of the high-affinity form of the enzyme. Similarly, after chronic, in vivo ingestion of ethanol, producing tolerance and physical dependence, only the properties of the neuronal enzyme are altered. Since only high concentrations of ethanol affect enzyme activity in vitro, and we found no potentiation of ethanol inhibition by norepinephrine, the role of enzyme inhibition in the actions of ethanol in the CNS remains open. However, the selective changes in enzyme activity reveal alterations in membrane lipid microdomains which may be associated with adaptive responses to ethanol. Monoamine oxidase (MAO) also exists in two forms, A and B. Ethanol selectively inhibits the B form of MAO in human platelet and brain membranes, by perturbation of lipids. In brains of C57B1 mice, but not alcohol-avoiding DBA mice, ethanol injection resulted in an increased level of phenylethylamine (PEA), a substrate of MAO-B which may be involved in reinforcement. Inhibition of MAO activity may therefore play a role in the physiological effects of ethanol, in addition to demonstrating the specificity of the biochemical effects of ethanol in the CNS. This project also included studies of glial regulation of neurotransmitter aspartate metabolism, adding to our understanding of mechanisms of regulation of neuronal activity.