Effects of ethanol and barbiturates on Ca2+-ATPase activity of erythrocyte and brain membranes.

Exposure to ethanol or pentobarbital in vitro stimulated the ATP-dependent efflux of calcium from human red blood cells (RBC) and the Ca2+-ATPase activity of RBC and rat brain synaptic plasma membranes (SPM). These effects were obtained with concentrations of ethanol (50 mM) and pentobarbital (60 microM) associated with intoxication in vivo. The enhancement of SPM Ca2+-ATPase by ethanol was due to an increase in the apparent affinity of the enzyme for calcium with no change in the maximum velocity. SPM Ca2+-ATPase was also stimulated by an unsaturated fatty acid, cis-vaccenic acid methyl ester (cis-VAME). The membrane-disordering effects of ethanol, four barbiturates and cis-VAME were evaluated in SPM using the fluorescent probe molecule 1,6-diphenyl-1,3,5-hexatriene (DPH). All the compounds decreased the fluorescence polarization of DPH, and these decreases were proportional to the increase in Ca2+-ATPase produced by these drugs. These findings suggest that the increase in Ca2+-ATPase and calcium efflux produced by ethanol and pentobarbital results from the membrane-disordering effects of these drugs.