THE IMIDAZOLE ANTIMYCOTICS ECONAZOLE AND MICONAZOLE REDUCE AGONIST-EVOKED PROTEIN-TYROSINE PHOSPHORYLATION AND EVOKE MEMBRANE DEPOLARIZATION IN HUMAN PLATELETS - CAUTIONS FOR THEIR USE IN STUDYING CA2+ SIGNALING PATHWAYS

In many cell types depletion of the intracellular Ca2+ stores promotes divalent cation entry across the plasma membrane, although the mechanism of such store-regulated Ca2+ entry remains unclear. It has been suggested that cytochrome P-450 plays a role in the communication from intracellular stores to plasma membrane in human platelets and other cells. These studies involved the use of the imidazole antimycotics, econazole and miconazole, which are inhibitors of cytochrome P-450. Here we report additional effects of the imadazole antimycotics, which we show to inhibit agonist-evoked protein-tyrosine phosphorylation and to evoke plasma membrane depolarisation in human platelets. Both of these effects might be expected to influence agonist-evoked Ca2+ entry in these and other cells. These data suggest that great caution is required in interpreting the results from studies using imadazole antimycotics and in particular imply that the effects of these inhibitors cannot be taken as evidence for a role for cytochrome P-450 in the Ca2+ entry pathway.