IMIDAZOLE ANTIMYCOTICS INHIBITORS OF CYTOCHROME-P450 INCREASE PHOSPHATIDYLSERINE SYNTHESIS SIMILARLY TO K+-CHANNEL BLOCKERS IN JURKAT T-CELLS

The imidazole antimycotics, miconazole, econazole and triclomazole as well as alpha-naphtoflavone, known as powerful inhibitors of cytochrome P450 and previously recognized as K+ channel blockers are shown to be potent activators of the base exchange enzyme system responsible for the biosynthesis of phosphatidylserine in Jurkat T cells. The inhibition of CD3-induced Ca2+ influx by antimycotics but not by K+ channel blockers, demonstrated that the rise in phosphatidylserine synthesis caused by the two classes of drugs, was independent of Ca2+ influx in the cells. In addition, we show that the action of these drugs on phosphatidylserine synthesis was not mimicked by modifications of membrane potential. The regulation of both K+ channels and the base exchange enzyme system thus occurs through a similar (or common) pathway that is independent of Ca2+-influx and membrane potential.