Submitted on August 14, 2008
Revised on October 5, 2008
Accepted on October 23, 2008
Pendrin in mouse kidney is primarily regulated by chloride excretion but also by systemic metabolic acidosis
Patricia Hafner1, Rosa Grimaldi2, Paola Capuano1, Giovambattista Capasso3, and Carsten A Wagner1*
1 University of Zurich
2 2nd University of Naples
3 Second University of Naples
* To whom correspondence should be addressed. E-mail: wagnerca{at}access.uzh.ch.
The chloride/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated. Pendrin abundance 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 chloride excretion and decreased upon chloride loading. Hence, it is unclear if pendrin regulation during NH4Cl induced acidosis is primarily due the chloride load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral chloride load and examined systemic acid-base status, urinary acidification, urinary chloride excretion, and pendrin abundance in kidney. NaCl or NH4Cl increased urinary Cl- excretion whereas (NH4)2SO4, Na2SO4 and acetazolamide treatments decreased urinary Cl- excretion. NH4Cl, (NH4)2SO4, and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH4Cl, and (NH4)2SO4 loading and increased with the other treatments. (NH4)2SO4 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 weeks on a low (20 %) and high protein (50 %) diet. High protein diet slightly increased urinary Cl- excretion, strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary chloride excretion but not blood chloride. However, metabolic acidosis caused by acetazolamide or (NH4)2SO4-loading prevented the increase or even reduced pendrin expression despite low urinary chloride excretion suggesting independent regulation by acid-base status.
