Genetic disorders of membrane transport -: II.: Regulation of CFTR by small molecules including HCO3-
Genetic disorders of membrane transport -: II.: Regulation of CFTR by small molecules including HCO3-
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DOI：
10.1152/ajpgi.1998.275.6.g1221
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发表时间：
1998-12-01
影响因子：
4.5
通讯作者：
Machen, TE
中科院分区：
文献类型：
--
作者：
Illek, B;Fischer, H;Machen, TE
囊性纤维化（CF）影响许多上皮组织，包括胃肠道中的上皮组织。这篇综述的目的是总结与各种小分子调控CF基因的蛋白产物CF跨膜传导调节因子（CFTR）相关的数据。人们对发现可以外源性添加到细胞和组织中以调节CFTR的小分子产生了浓厚的兴趣，这些小分子可能单独使用或与遗传方法结合用于CF治疗。我们将讨论染料木黄酮，米力农，8-环戊基-1，3-二丙基黄嘌呤，IBMX和NS-004的作用的明显机制，其中几个似乎直接与CFTR的一个或两个核苷酸结合域相互作用。我们还讨论了HCO3-如何与CFTR相互作用，作为渗透阴离子和Cl-渗透通过CFTR离子通道的潜在调节剂。这是可能的，有复杂的相互作用之间的Cl-和HCO3-在分泌的两种离子通过CFTR和阴离子交换在肠细胞中，这些可能产生的作用CFTR在调节肠道HCO3-分泌以及内部和细胞外的pH值。
Cystic fibrosis (CF) affects a number of epithelial tissues, including those in the gastrointestinal tract. The goal of this review is to summarize data related to regulation of the protein product of the CF gene, CF transmembrane conductance regulator (CFTR), by a variety of small molecules. There has been a surge of interest in discovering small molecules that could be exogenously added to cells and tissues to regulate CFTR and could potentially be used alone or in combination with genetic approaches for therapy in CF. We will discuss the apparent mechanisms of action of genistein, milrinone, 8-cyclopentyl-1,3-dipropylxanthine, IBMX, and NS-004; several of which appear to interact directly with one or both nucleotide binding domains of CFTR. We also discuss how HCO3- interacts with CFTR as both a permeating anion and a potential regulator of Cl- permeation through the CFTR ion channel. It is likely that there are complicated interactions between Cl- and HCO3- in the secretion of both ions through the CFTR and the anion exchanger in intestinal cells, and these may yield a role of CFTR in regulation of intestinal HCO3- secretion as well as of intra- and extracellular pH.