Plasma membrane lipid composition modulates action of anesthetics.

The effect of LM fibroblast plasma membrane phospholipid composition on the selectivity of charged amphipathic anesthetics for exofacial or cytofacial leaflets was examined. Because preference of charged amphipaths for one of the plasma membrane bilayer leaflets may be conferred by net changes in the polar headgroup composition, LM fibroblasts were cultured in the presence of choline or N-demethylated analogs in order to change this polar headgroup composition. These altered bases were incorporated into plasma membrane phospholipids. A significant difference in 1,6-diphenyl-1,3,5-hexatriene (DPH) limiting anisotropy was observed between plasma membrane leaflets of phosphatidylcholine-, but not phosphatidylethanolamine-enriched cells. Phenobarbital, which preferentially decreased the limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene in the exofacial leaflet, had little or no preferential effect in phosphatidyl-N,N-dimethylethanolamine-enriched membranes. Prilocaine preferentially reduced the limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene in the exofacial leaflet in phosphatidyl-N-methylethanolamine-enriched membranes, exactly opposite to its effect in phosphatidylcholine-enriched membranes. In contrast, prilocaine had no selective effect in phosphatidylethanolamine-enriched membranes. In summary, the phospholipid polar headgroup composition can dramatically affect the selectivity of charged amphipathic anesthetics in altering the limiting anisotropy, a measure of restriction to motion of 1,6-diphenyl-1,3,5-hexatriene, in individual monolayers.