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
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.
- Research Organization:
- Diabetes and Atherosclerosis Research, Upjohn Company, Kalamazoo, Michigan
- OSTI ID:
- 5442683
- Journal Information:
- Exp. Mol. Pathol.; (United States), Vol. 38:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORPROMAZINE
BIOLOGICAL EFFECTS
LIPIDS
METABOLISM
AORTA
BIOSYNTHESIS
CARBON 14
CHOLESTEROL
IN VITRO
LABELLED COMPOUNDS
PHOSPHOLIPIDS
RABBITS
RATS
STEROLS
TRACER TECHNIQUES
AMINES
ANIMALS
ARTERIES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARBON ISOTOPES
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ESTERS
EVEN-EVEN NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PHENOTHIAZINES
PSYCHOTROPIC DRUGS
RADIOISOTOPES
RODENTS
STEROIDS
SYNTHESIS
TRANQUILIZERS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550501* - Metabolism- Tracer Techniques