The Role of Pendrin in Renal Physiology

Pendrin is a Na+-independent Cl−/HCO3− 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 HCO3− secretion primarily through pendrin-mediated Cl−/HCO3− exchange. At least in some treatment models, pendrin acts in tandem with the Na+-dependent Cl−/HCO3− exchanger (NDCBE) encoded by Slc4a8 to mediate NaCl absorption. The pendrin-mediated Cl−/HCO3− exchange process is greatly upregulated in models of metabolic alkalosis, such as following aldosterone administration or dietary NaHCO3 loading. It is also upregulated by angiotensin II. In the absence of pendrin [Slc26a4 (−/−) 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. ...