Phosphatidylinositol from ethanol-fed rats confers membrane tolerance to ethanol

The presence of ethanol disorders (fluidizes) biological membranes, but its chronic administration confers resistance to this perturbation (membrane tolerance). The latter effect has been invoked as an explanation for behavioral tolerance in alcoholics, but the molecular basis for membrane tolerance is obscure. To study the molecular mechanisms of this acquired resistance to disordering, we fed rats ethanol (36% of total calories) for 35 days, after which we quantitatively separated the phospholipids of hepatic microsomal membranes by high-performance liquid chromatography. Multilamellar vesicles were prepared from the recombined phospholipid classes, and their physical properties were examined by electron spin resonance. Vesicles composed of phospholipids from untreated rats were disordered (fluidized) in the presence of ethanol, whereas those made from phospholipids of ethanol-fed rats were resistant to this effect. When phosphatidylcholine (66.5 mol %), phosphatidylethanolamine (21 mol %), or phosphatidylserine (4.0 mol %) from ethanol-fed rats replaced their corresponding phospholipids in vesicles prepared from microsomal phospholipids from untreated rats, the membranes were still disordered by ethanol. In contrast, when 2.5-8.5 mol % phosphatidylinositol from ethanol-fed rats replaced phosphatidylinositol from untreated rats, the reconstituted membranes were rendered resistant to ethanol-induced disordering. Liver microsomal phosphatidylinositol (2.5-8.5 mol %) from ethanol-fed rats also conferred membrane tolerance to vesicles composed of bovine liver and brain phospholipids, an effect which demonstrates that the ability of phosphatidylinositol to confer membrane tolerance is not restricted to the microsomal membrane.