Drug-induced surface membrane phospholipid composition in murine fibroblasts

The effects of drug on phospholipid composition of cell surface membranes are not well understood at this time. The effects of membrane-active drugs and membrane depolarization on the phospholipid composition were determined in murine LM fibroblasts. Receptor-aggregating drugs such as concanavalin A and cytoskeleton-disrupting agents such as colchicine, vinblastine, and cytochalasin B decreased phosphatidylserine content of the plasma membrane from 5.4 +/- 1.5% to as low as 1.4 +/- 0.2%. In addition, concanavalin A and colchicine increased the phosphatidylglycerol content from 6.9 +/- 1.6% to 13.1 +/- 0.7% and 10.6 +/-1.7%, respectively, while vinblastine and cytochalasin B had no effect. Pentobarbital decreased the content of phosphatidylinositol+ phosphatidylserine and of phosphatidylglycerol almost 2-fold. Propranolol, ethanol, and depolarization with 120 mM KCl had small or ne effects on plasma membrane phospholipid composition. None of the above drugs or treatments significantly altered the asymmetric distribution of phosphatidylethanolamine across the LM cell plasma membrane under the conditions tested. In addition, energy inhibitors that deplete the proton-motive force of the cell (NaN3 and KCN) and inhibitors of ATP synthesis such as NaAsO4 did not affect the asymmetric distribution of phosphatidylethanolamine. It is concluded that the mechanism of action of membrane-active drugs such as concanavalin A, vinblastine, colchicine and pentobarbital may involve alterations in plasma membrane composition. It also appears that microfilaments, microtubules, beta-adrenergic receptors, membrane fluidity, and membrane potential are not critical for the regulation of the asymmetric distribution of membrane phosphatidylethanolamine.