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 Ca(2+)-influx and membrane potential.
Aussel
C
C
INSERM U343, Interactions cellulaires en Immunologie, Faculté de Médecine, Nice, France.
Breittmayer
J P
JP
D000935:Antifungal Agents / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D017252:CD3 Complex / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003022:Clotrimazole / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004464:Econazole / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008825:Miconazole / Q000494:pharmacology; D010718:Phosphatidylserines / Q000096:biosynthesis*; D015221:Potassium Channels / Q000187:drug effects*; D012694:Serine / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology
D000935:Antifungal Agents; D001571:Benzoflavones; D017252:CD3 Complex; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D010718:Phosphatidylserines; D015221:Potassium Channels; D014634:Valinomycin; D012694:Serine; C011512:alpha-naphthoflavone; D004464:Econazole; D008825:Miconazole; D003022:Clotrimazole; D002118:Calcium