Effects of phenothiazines on low density lipoprotein metabolism in cultured human fibroblasts.
Treatment of cultured human fibroblasts with trifluoperazine or chlorpromazine resulted in a biphasic effect on low density lipoprotein (LDL) catabolism, depending upon the dose. At up to 10(-5) M, a marked increase in LDL binding, internalization and degradation was observed. This phenomenon took place within the first hours of incubation with the drugs, suggesting a direct effect on cell membrane physical characteristics, probably related to the lipophilic properties of phenothiazines. Concentrations above 2 X 10(-5) M resulted in a relative decrease in LDL binding and internalization, and in a dramatic decrease in LDL degradation, which may be related to an inhibition of calmodulin-dependent processes.
D002147:Calmodulin / Q000502:physiology; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010640:Phenothiazines / Q000494:pharmacology*; D012995:Solubility; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D008077:Lipoproteins, LDL; D010640:Phenothiazines; D014268:Trifluoperazine; D002746:Chlorpromazine