Pendrin in the mouse kidney is primarily regulated by Cl- excretion but also by systemic metabolic acidosis

Hafner P, Grimaldi R, Capuano P, Capasso G, Wagner CA. Pendrin in the mouse kidney is primarily regulated by Cl- excretion but also by systemic metabolic acidosis. Am J Physiol Cell Physiol 295: C1658-C1667, 2008; doi:10.1152/ajpcell.00419.2008.-The Cl-/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated cells. The abundance of pendrin is reduced during metabolic acidosis induced by oral NH4Cl loading. More recently, it has been shown that pendrin expression is increased during conditions associated with decreased urinary Cl- excretion and decreased upon Cl- loading. Hence, it is unclear if pendrin regulation during NH4Cl-induced acidosis is primarily due the Cl- load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral Cl- load and examined the systemic acid-base status, urinary acidification, urinary Cl- excretion, and pendrin abundance in the kidney. NaCl or NH4Cl increased urinary Cl- excretion, whereas (NH4)(2)SO4, Na2SO4, and acetazolamide treatments decreased urinary Cl- excretion. NH4Cl, (NH4)(2)SO4, and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH4Cl, and (NH4)(2)SO4 loading and increased with the other treatments. (NH4)(2)SO4 and acetazolamide treatments reduced the relative number of pendrin-expressing cells in the collecting duct. In a second series, animals were kept for 1 and 2 wk on a low-protein (20%) diet or a high-protein (50%) diet. The high-protein diet slightly increased urinary Cl- excretion and strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary Cl- excretion but not blood Cl-. However, metabolic acidosis caused by acetazolamide or (NH4)(2)SO4 loading prevented the increase or even reduced pendrin expression despite low urinary Cl- excretion, suggesting an independent regulation by acid-base status.