酮康唑可激活氯离子传导，并阻断培养的囊性纤维化（CFPAC-1）细胞对氯离子和液体的吸收。
Ketoconazole activates Cl- conductance and blocks Cl- and fluid absorption by cultured cystic fibrosis (CFPAC-1) cells.
作者信息
Kersting U, Kersting D, Spring K R
机构信息
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
出版信息
Proc Natl Acad Sci U S A. 1993 May 1;90(9):4047-51. doi: 10.1073/pnas.90.9.4047.
Abstract
The role of arachidonic acid metabolites in the regulation of apical cell membrane Cl- conductance and transepithelial transport of fluid and Cl- by cultured pancreatic cells from cystic fibrosis (CFPAC-1) and corrected (PAC-1) cell lines was evaluated by the use of inhibitors. CFPAC-1 cells did not exhibit an apical membrane Cl- conductance, absorbed Cl- and fluid, and did not respond to stimulation or inhibition of cAMP action. PAC-1 cells exhibited a cAMP-responsive apical Cl- conductance, which was blocked by indomethacin, a cyclooxygenase inhibitor. Ketoconazole, an epoxygenase inhibitor, had virtually no effects on PAC-1 cell Cl- conductance but caused CFPAC-1 cells to develop a cAMP-insensitive Cl- conductance, blocked Cl- and fluid absorption, and reduced transepithelial electrical resistance. Ketoconazole treatment effectively reversed the cystic fibrosis defect in these cultured cells.
摘要
通过使用抑制剂，评估了花生四烯酸代谢产物在调节来自囊性纤维化（CFPAC-1）和校正（PAC-1）细胞系的培养胰腺细胞顶质膜氯离子电导率以及液体和氯离子跨上皮转运中的作用。CFPAC-1细胞未表现出顶质膜氯离子电导率，吸收氯离子和液体，并且对cAMP作用的刺激或抑制无反应。PAC-1细胞表现出对cAMP有反应的顶质膜氯离子电导率，该电导率被环氧化酶抑制剂吲哚美辛阻断。环氧合酶抑制剂酮康唑对PAC-1细胞的氯离子电导率几乎没有影响，但使CFPAC-1细胞产生对cAMP不敏感的氯离子电导率，阻断了氯离子和液体吸收，并降低了跨上皮电阻。酮康唑处理有效地逆转了这些培养细胞中的囊性纤维化缺陷。
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