Effects of chlorpromazine and trifluoperazine on choline metabolism and phosphatidylcholine biosynthesis in cultured chick heart cells under normoxic and anoxic conditions.
The effects of chlorpromazine and trifluoperazine on phosphatidylcholine biosynthesis in the heart were investigated in isolated cardiac cells under normoxic and anoxic conditions. The cells were obtained from 7-day-old chick embryos and were maintained in culture. After 96 hr, cells were maintained either in an incubator with oxygen at room air concentration (normoxia) or in an incubator containing 95% nitrogen and 5% CO2 (anoxia). Pulse chase experiments with [methyl-3H]choline were conducted using a 2-hr incubation with choline. Chlorpromazine and trifluoperazine at 10(-5) M produced a significant (P less than 0.05) increase in the incorporation of choline into both phosphocholine and phospholipid. High concentrations of chlorpromazine or trifluoperazine i.e. 10(-4) M, damaged myocardial cells as reflected in a significant (P less than 0.05) reduction in cellular protein and a further reduction in labelled choline in phosphocholine or phospholipid after adjusting for the lower protein concentrations. Anoxia altered choline metabolism but 6 hr of anoxia was the minimum time needed for the effect to be observable. Anoxia, for 24 hr, produced a significant (P less than 0.05) reduction in labelled choline in phosphocholine without a significant change in incorporation of label in phospholipid or cellular protein. Both chlorpromazine and trifluoperazine at 10(-5) M prevented anoxic-induced changes in phosphocholine metabolism. Thus, chlorpromazine and trifluoperazine affect phospholipid biosynthesis in cardiac cells and prevent anoxia-induced changes in phosphatidylcholine biosynthesis.
Rabkin
S W
SW
Department of Medicine, University of British Columbia, Vancouver, Canada.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002746:Chlorpromazine / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010100:Oxygen / Q000502:physiology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D014268:Trifluoperazine / Q000494:pharmacology*
D010713:Phosphatidylcholines; D014268:Trifluoperazine; D002794:Choline; D010100:Oxygen; D002746:Chlorpromazine