Pendrin is a Na+-independent Cl/HCO exchanger that localizes to type B and non-A, non-B intercalated cells, which are expressed within the aldosterone-sensitive region of the nephron, i.e., the distal convoluted tubule, the connecting tubule, and the cortical collecting duct. Type B cells mediate Cl absorption and HCO secretion primarily through pendrin-mediated Cl/HCO exchange. At least in some treatment models, pendrin acts in tandem with the Na+-dependent Cl/HCO exchanger (NDCBE) encoded by to mediate NaCl absorption. The pendrin-mediated Cl/HCO exchange process is greatly upregulated in models of metabolic alkalosis, such as following aldosterone administration or dietary NaHCO loading. It is also upregulated by angiotensin II. In the absence of pendrin [ (−/−) or pendrin null mice], aldosterone-stimulated NaCl absorption is reduced, which lowers the blood pressure response to aldosterone and enhances the alkalosis that follows the administration of this steroid hormone. Pendrin modulates aldosterone-induced Na+ absorption by changing ENaC abundance and function through a kidney-specific mechanism that does not involve changes in the concentration of a circulating hormone. Instead, pendrin changes ENaC abundance and function at least in part by altering luminal HCO and ATP concentrations. Thus, aldosterone and angiotensin II also stimulate pendrin expression and function, which likely contributes to the pressor response of these hormones. This review summarizes the contribution of the Cl/HCO exchanger pendrin in distal nephron function.


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