ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

乙醇扰乱神经元膜脂结构及其中枢神经系统 由于功能的改变，可能会产生继发性的影响 膜结合酶。高浓度的乙醇会抑制大脑 (Na-+，K-+)ATPase活性，我们发现对小鼠有抑制作用 酒精对突触体ATPase活性的影响不完全依赖于 与膜脂的相互作用；乙醇也可能直接与 蛋白质。我们的研究表明去甲肾上腺素不会增强 乙醇对小鼠和大鼠脑内ATPase的抑制作用。自.以来 只有在乙醇浓度较高时，活性才会受到实质性的抑制 浓度，酶抑制本身在中枢神经系统活动中的作用 乙醇仍然值得商榷。然而，ATPase的其他方面 活性可以作为膜结构变化的探针，如下所示 酒精暴露，这可能与耐受性或身体状况有关 依赖。 ATPase在大脑中以两种形式存在，对 抑制剂哇巴因。高亲和力成分被认为是 定位于神经细胞膜。在慢性乙醇治疗之后， 该组分对哇巴因的亲和力选择性增加， 很可能是由于这种形式的脂质微域的变化造成的 这种酶。另一种膜结合酶，单胺氧化酶(MAO)，也 以A和B两种形式存在乙醇选择性地抑制B形式 膜微扰引起的人脑和血小板组织中的酶 血脂，支持两种形式的MAO是 以它们的脂肪环境来区分。乙醇在50 mm处显著 抑制酶活性，抑制MAO-B可能在 介导乙醇对中枢神经系统的影响。该项目还包括研究 神经递质代谢的神经胶质调节，增加了我们的 了解神经元活动调节的基本机制。

Ethanol perturbs the structure of neuronal membrane lipids, and its CNS effects may arise secondarily as a result of changes in the function of membrane-bound enzymes. At high concentrations ethanol inhibits brain (Na-+, K-+) ATPase activity, and we found that inhibition of mouse synaptosomal ATPase activity by alcohols does not depend solely on interactions with membrane lipids; ethanol may also interact directly with the protein. Our studies showed no potentiation by norepinephrine of ethanol-induced inhibition of ATPase in mouse or rat brain. Since substantial inhibition of activity occurs only at high ethanol concentrations, the role of enzyme inhibition per se in the CNS actions of ethanol remains open to question. However, other aspects of ATPase activity can serve as a probe of changes in membrane structure, following ethanol exposure, which may be associated with tolerance or physical dependence. ATPase exists in two forms in the brain, with high and low affinity for the inhibitor, ouabain. The high-affinity component is believed to be localized in neuronal membranes. Following chronic ethanol treatment, there was a selective increase in affinity for ouabain of this component, most likely resulting from changes in the lipid microdomain of this form of the enzyme. Another membrane-bound enzyme, monoamine oxidase (MAO), also exists in two forms, A and B. Ethanol selectively inhibited the B form of the enzyme in human brain and platelet tissue by perturbation of membrane lipids, supporting the hypothesis that the two forms of MAO are distinguished by their lipid environments. Ethanol at 50 mM significantly inhibited enzyme activity, and inhibition of MAO-B could play a role in mediating the CNS effects of ethanol. This project also included studies of glial regulation of neurotransmitter metabolism, adding to our understanding of basic mechanisms of regulation of neuronal activity.