title: Effect of chlorpromazine on lipid metabolism in aortas from cholesterol-fed rabbits and normal rats, in vitro: inhibition of sterol esterification and modification of phospholipid synthesis.
abstract: Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in isolated arterial microsomes and in intact arterial tissue from the rat and cholesterol-fed rabbit in vitro. In isolated rabbit arterial microsomes, CPZ resulted in a concentration-dependent inhibition of ACAT with 50% inhibition of [1-14C]oleoylCoA incorporation into [14C]cholesteryl esters occurring at 0.1 mM CPZ. CPZ also effectively inhibited the incorporation of [14C]oleate into triglycerides without affecting incorporation into diglycerides. Additionally, CPZ altered the pattern of arterial phospholipids synthesized from [1-14C]oleate. Incorporation into phosphatidylcholine was depressed while incorporation into phosphatidylinositol was increased. Since diglyceride synthesis appeared to be unaffected by CPZ, a redirection of phosphatidic acid into the CDP-diglyceride pathway of glycerolipid synthesis does not adequately account for the effect of CPZ on arterial phospholipid and triglyceride synthesis in these experiments.
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D002250:Carbon Radioisotopes; D002746:Chlorpromazine / Q000494:pharmacology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D050356:Lipid Metabolism; D008297:Male; D009829:Oleic Acids / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D011817:Rabbits; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
chemical_list: D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary; D009829:Oleic Acids; D010743:Phospholipids; D002785:Sterol O-Acyltransferase; D002746:Chlorpromazine