MOLECULAR-CLONING AND EXPRESSION OF A CYCLIC AMP-ACTIVATED CHLORIDE CONDUCTANCE REGULATOR - A NOVEL ATP-BINDING CASSETTE TRANSPORTER

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-r egulated, cAMP-activated chloride channel located in the apical membra ne of many epithelial secretory cells. Here we report cloning of a cAM P-activated epithelial basolateral chloride conductance regulator (EBC R) that appears to be a basolateral CFTR counterpart. This novel chlor ide channel or regulator shows 49% identity with multidrug resistance- associated protein (MRP) and 29% identity with CFTR. On expression in Xenopus oocytes, EBCR confers a cAMP-activated chloride conductance th at is inhibited by the chloride channel blockers niflumic acid, 5-nitr o-2-(3-phenylpropylamine)benzoic acid, and 4,4'-diisothiocyanatostilbe ne-2,2'-disulfonic acid. Northern blot analysis reveals high expressio n in small intestine, kidney, and liver. In kidney, immunohistochemist ry shows a conspicuous basolateral localization mainly in the thick as cending limb of Henle's loop, distal convoluted tubules and to a lesse r extent connecting tubules. These data suggest that in the kidney EBC R is involved in hormone-regulated chloride reabsorption.