Effect of chlorpromazine administration on enzyme activity concerning phosphatidic acid metabolism in rat liver.

The effect of chlorpromazine on phospholipid metabolism was studied in rat liver endoplasmic reticulum. Administration of chlorpromazine per os caused a marked increase in microsomal phospholipid content without affecting its composition. The rate of incorporation of both [(32)P]orthophosphate and [2-(3)H)glycerol into phosphatidic acid and phosphatidylinositol increased by the administration of chlorpromazine. Enhanced labeling of phosphatidylinositol was also observed when myo-[2-(3)H]inositol was used as a precursor. The activity of glycerophosphate acyltransferase significantly increased and that of phosphatidate phosphohydrolase markedly decreased by the administration of chlorpromazine. The activity of phosphatidate cytidylyltransferase was not affected by the drug treatment. These findings suggested that the administration of chlorpromazine increases the availability of phosphatidic acid by activating glycerophosphate acyltransferase and inhibiting phosphatidate phosphohydrolase, leading to enhanced synthesis of phosphatidylinositol.