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

1 Institute of Physiology and Center for Human Integrative Physiology, University of Zurich, Zurich, Switzerland; and 2 School of Medicine, Second University of Naples, Naples, Italy Submitted 14 August 2008 ; accepted in final form 23 October 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 NH 4 Cl 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 NH 4 Cl-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 NH 4 Cl increased urinary Cl – excretion, whereas (NH 4 ) 2 SO 4 , Na 2 SO 4 , and acetazolamide treatments decreased urinary Cl – excretion. NH 4 Cl, (NH 4 ) 2 SO 4 , and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH 4 Cl, and (NH 4 ) 2 SO 4 loading and increased with the other treatments. (NH 4 ) 2 SO 4 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 (NH 4 ) 2 SO 4 loading prevented the increase or even reduced pendrin expression despite low urinary Cl – excretion, suggesting an independent regulation by acid-base status. transporter; collecting duct Address for reprint requests and other correspondence: C. A. Wagner, Institute of Physiology and Zurich Center for Integrative Human Physiology, Univ. of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland (e-mail: Wagnerca{at}access.unizh.ch )