Effects of ethanol and related drugs on the physical and functional properties of brain membranes.
The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was incorporated into myelin and synaptic plasma membrane fractions prepared from mouse brain. The absorption-corrected fluorescence and polarization of the fluorescent probe a molecule and the membrane absorbance were measured simultaneously, using a computer-centered spectrofluorimeter. In vitro exposure of synaptic membranes to ethanol (25-100 mM) decreased all three parameters in a dose-dependent manner. The order of sensitivity was: corrected fluorescence greater than or equal to polarization much greater than absorbance. Myelin was not affected by these concentrations of ethanol, indicating a selective effect on synaptic membranes. The polarization of fluorescence of DPH in synaptic membranes was also decreased by tert-butanol, pentobarbital, and cis- and trans-vaccinic acid. The results suggest that ethanol and related drugs perturb the hydrophobic interior of synaptic membranes. These compounds also increased the exposure of synaptic sulfhydryl groups and inhibited the depolarization- and ATP-dependent uptake of calcium by synaptosomal preparations. These results suggest that the perturbation altered the conformation of synaptic proteins and inhibited the transport of calcium by synaptosomal membranes.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D000440:Butanols / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004161:Diphenylhexatriene / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009186:Myelin Sheath / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects*; D020002:tert-Butyl Alcohol
D000440:Butanols; D005456:Fluorescent Dyes; D013438:Sulfhydryl Compounds; D004161:Diphenylhexatriene; D000431:Ethanol; D010424:Pentobarbital; D020002:tert-Butyl Alcohol; D002118:Calcium