ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

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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.