ACUTE ETHANOL DECREASES NMR RELAXATION-TIMES OF WATER HYDROGEN PROTONS IN FISH BRAIN

The traditional belief about ethanol's mechanism of action is based on ethanol's lipophilicity and capability to penetrate and disorder lipi d bilayers. This traditional belief is now being supplanted by growing evidence that ethanol has relatively selective actions on certain syn aptic receptors, such as those for NMDA, serotonin, and GABA. It was r ecently argued that these receptor specificities are secondary to a pr eferential ability of ethanol to displace membrane bound water in the domains of certain receptors. The data obtained in this study are cons istent with the original hypothesis: any disorganization of cellular w ater by ethanol will be detectable by proton nuclear magnetic resonanc e (NMR) spectroscopy. In particular, the relaxation times of water hyd rogen protons reflect how constrained water molecules are by the macro molecules within cells. The relaxation time of ''bulk'' water is lengt hened relative to water molecules that are under the influence of elec tromagnetic fields of macromolecular surfaces within cells. Here, we t ested this hypothesis in living fish, which dosed themselves by swimmi ng in water that had added ethanol. Estimates of brain alcohol at 5 mi n after initial exposure revealed that the brain concentration was onl y about 1/3 that of the water in which they were swimming. The average value of the NMR relaxation time T-1, but not T-2, was decreased at 5 min (when brain concentrations were on the order of 100 mM) and reach ed statistical significance at 10 and 30 min after initial exposure. W e conclude that these NMR results add to the growing evidence that acu te ethanol acts by affecting hydrogen-bonded water at membranes and ma cromolecular surfaces within brain cells. Changes in the organization of cellular water as well as the conformation of macromolecules in the membrane and cytoplasm seem obvious. This mechanism would seem to pro vide a parsimonious explanation for the high sensitivity that a variet y of receptor subtypes seem to have for ethanol.