ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

据推测，乙醇在中枢神经系统中的作用源于

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.