Effect of chlorpromazine associated with liposomes on the biosynthesis of acidic lipids in subcellular membranes.

Abstract

The study examined the effect of an association of chlorpromazine, phosphatidic acid and cytidine-diphosphoryl-1,2-diglycerides (CDP-diglycerides) with small unilamellar lecithin liposomes on the formation, hydrolysis and transfer of lipids and cytidine liponucleotides in microsomal and mitochondrial membranes isolated from guinea-pig liver. Association with liposomes undermined the effect of chlorpromazine on these processes, but the type of effect, i.e. inhibitory or stimulatory, was retained. Association of CDP-diglycerides with small unilamellar lecithin liposomes tended to protect this substrate from subcellular uptake, thereby inhibiting phosphatidylinositol and polyglycerophosphatide formation. Phosphatidic acid in the form of liposomes stimulated CDP-diglyceride formation. The nature of fatty acids influenced the magnitude of these effects in polyglycerophosphatide biosynthesis. Transfer of CDP-diglycerides from microsomal to mitochondrial membranes was inhibited by both chlorpromazine associated with liposomes and liposomes alone.