Trifluoperazine increases fatty acid turnover in phospholipids in cultured human fibroblasts.
A 24-hr pretreatment of cultured human fibroblasts with trifluoperazine induced a marked increase in incorporation of saturated (stearic, palmitic) and unsaturated (oleic, arachidonic) fatty acids into phospholipids (1.5- to 2-fold for 5.10(-5) M trifluoperazine). Concomitantly, incorporation into cholesteryl esters was strongly inhibited (20% of control for 5.10(-5) M trifluoperazine). The drug did not change the phospholipid composition of treated cells. The effect of trifluoperazine on oleic acid incorporation into phospholipids was time-dependent and reached a maximum after a six-hr preincubation with the drug. Trifluoperazine also induced an increase in the rate of chase of oleic acid from the different phospholipid classes. In vitro preincubation of cell-free extracts with trifluoperazine resulted in activation of phospholipid acyltransferases, whereas cholesterol acyltransferase activity was decreased. The rapid effect of trifluoperazine together with its effect on a cell-free system suggests a direct action of this amphiphilic drug on the acyltransferase activities, probably by modification of the structural organization of cellular membranes.
Mazière
C
C
Laboratoire de Chimie Biologique, Faculté de Medecine Saint Antoine, Paris, France.
Mazière
J C
JC
Mora
L
L
Auclair
M
M
Polonovski
J
J
D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis*; D014268:Trifluoperazine / Q000494:pharmacology*
D002788:Cholesterol Esters; D005227:Fatty Acids; D009829:Oleic Acids; D010743:Phospholipids; D014268:Trifluoperazine; D019301:Oleic Acid