Hornstein E H, Vassilopoulos D, Thomas D E, Friedman F K, Tsokos G C
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Immunopharmacol Immunotoxicol. 1996 May;18(2):237-45. doi: 10.3109/08923979609052734.
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.
研究了细胞色素P - 450在细胞内钙离子对人外周血T淋巴细胞质膜钙离子通透性调节中的作用。我们评估了细胞色素P - 450的咪唑类抑制剂对使用微粒体ATP酶抑制剂毒胡萝卜素（THG）耗尽细胞内钙离子储存所产生的细胞质游离钙离子（[Ca + 2]i）反应的影响。益康唑、咪康唑和克霉唑显著抑制了THG介导的[Ca + 2]i增加，并且自身诱导了[Ca + 2]i增加。这种抑制作用先前在其他细胞系统中观察到，并归因于这些药物对细胞色素P - 450的抑制。然而，我们评估了多种结构不同的P - 450抑制剂，发现没有一种影响[Ca + 2]i，这表明咪唑类药物的作用机制不涉及P - 450。
