Modulation of human T-lymphocyte plasma membrane Ca2+ permeability by imidazole antimycotics.
The role of cytochrome P-450 in the regulation of plasma membrane Ca+2 permeability of human peripheral T-lymphocytes by intracellular Ca+2 was examined. We assessed the effect of imidazole inhibitors of cytochrome P-450 on the intracytoplasmic free Ca+2 ([Ca+2]i) response generated using the microsomal ATPase inhibitor thapsigargin (THG) to deplete the intracellular Ca+2 stores. Econazole, miconazole and clotrimazole dramatically inhibited the THG mediated increase in [Ca+2]i and induced an increase in [Ca+2]i themselves. This inhibitory effect was previously observed in other cell systems and was attributed to inhibition of cytochrome P-450 by these agents. However, we evaluated a variety of structurally dissimilar P-450 inhibitors and found that none affected [Ca+2]i, indicating that the mechanism of imidazole action does not involve P-450.
Hornstein
E H
EH
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Vassilopoulos
D
D
Thomas
D E
DE
Friedman
F K
FK
Tsokos
G C
GC
D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003022:Clotrimazole / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004464:Econazole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008825:Miconazole / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019284:Thapsigargin; D004464:Econazole; D008825:Miconazole; D003022:Clotrimazole; D002118:Calcium