多药耐药相关蛋白抑制剂对CFTR依赖性氯离子电流的阻断作用
Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins.
作者信息
Diena Tullia, Melani Raffaella, Caci Emanuela, Pedemonte Nicoletta, Sondo Elvira, Zegarra-Moran Olga, Galietta Luis J V
机构信息
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, and Centro di Biotecnologie Avanzate, 16148 Genoa, Italy.
出版信息
Eur J Pharmacol. 2007 Apr 10;560(2-3):127-31. doi: 10.1016/j.ejphar.2007.01.051. Epub 2007 Feb 3.
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that belongs to the same family as multidrug resistance-associated proteins whose main function is to expel xenobiotics and physiological organic anions from the cell interior. Despite the overall structural similarity with these membrane proteins, CFTR is not an active transporter but is instead a Cl- channel. We have tested the ability of known inhibitors of multidrug resistance-associated proteins to affect CFTR Cl- currents. We have found that sulfinpyrazone, probenecid, and benzbromarone are also inhibitors of CFTR activity, with a mechanism involving blockage of the channel pore.
摘要
囊性纤维化跨膜传导调节因子（CFTR）是一种膜蛋白，与多药耐药相关蛋白属于同一家族，其主要功能是将异生物素和生理性有机阴离子从细胞内排出。尽管与这些膜蛋白在整体结构上相似，但CFTR不是一种主动转运蛋白，而是一种氯离子通道。我们测试了已知的多药耐药相关蛋白抑制剂影响CFTR氯离子电流的能力。我们发现，磺吡酮、丙磺舒和苯溴马隆也是CFTR活性的抑制剂，其作用机制涉及通道孔的阻断。
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