Alvarez J, Montero M, Garcia-Sancho J
Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid, Spain.
J Biol Chem. 1992 Jun 15;267(17):11789-93.
The Ca(2+)-dependent K+ channel of human red cells was inhibited with high affinity by several imidazole antimycotics which are potent inhibitors of cytochrome P-450. IC50 values were (in microM): clotrimazole, 0.05; tioconazole, 0.3; miconazole, 1.5; econazole, 1.8. Inhibition of the channel was also found with other drugs with known cytochrome P-450 inhibitory effect. However, no inhibition was obtained with carbon monoxide (CO). This suggests that, given the high selectivity of the above inhibitors for the heme moiety, a different but closely related to cytochrome P-450 kind of hemoprotein may be involved in the regulation of the red cell Ca(2+)-dependent K+ channel. Clotrimazole also inhibited two other charybdotoxin-sensitive Ca(2+)-dependent K+ channels, those of rat thymocytes (IC50 = 0.1-0.2 microM) and of Ehrlich ascites tumor cells (IC50 = 0.5 microM). Imidazole antimycotics inhibit also receptor-operated Ca2+ channels (Montero, M., Alvarez, J. and García-Sancho, J. (1991) Biochem. J. 277, 73-79). This suggests that both Ca2+ and Ca(2+)-dependent K+ channels might have a similar regulatory mechanism involving a cytochrome.
几种咪唑类抗真菌药对人红细胞的钙依赖性钾通道具有高亲和力抑制作用，这些药物是细胞色素P - 450的有效抑制剂。半数抑制浓度（IC50）值（以微摩尔计）分别为：克霉唑0.05；噻康唑0.3；咪康唑1.5；益康唑1.8。在其他已知具有细胞色素P - 450抑制作用的药物中也发现了对该通道的抑制作用。然而，一氧化碳（CO）未产生抑制作用。这表明，鉴于上述抑制剂对血红素部分具有高选择性，可能有一种与细胞色素P - 450不同但密切相关的血红蛋白参与红细胞钙依赖性钾通道的调节。克霉唑还抑制了其他两种对蝎毒素敏感的钙依赖性钾通道，即大鼠胸腺细胞的通道（IC50 = 0.1 - 0.2微摩尔）和艾氏腹水瘤细胞的通道（IC50 = 0.5微摩尔）。咪唑类抗真菌药也抑制受体操纵的钙通道（蒙特罗，M.，阿尔瓦雷斯，J.和加西亚 - 桑乔，J.（1991年）《生物化学杂志》277，73 - 79）。这表明钙通道和钙依赖性钾通道可能具有相似的涉及细胞色素的调节机制。
