title: Pendrin in the mouse kidney is primarily regulated by Cl- excretion but also by systemic metabolic acidosis.
abstract: 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.
authors.affiliation: Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hafner
authors.forename: Rosa
authors.initials: R
authors.lastname: Grimaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Capuano
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
mesh_terms: D000086:Acetazolamide / Q000633:toxicity; D000136:Acid-Base Equilibrium / Q000502:physiology*; D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000643:Ammonium Chloride / Q000633:toxicity; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002712:Chlorides / Q000032:analysis*; D004232:Diuretics / Q000633:toxicity; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D002712:Chlorides; D004232:Diuretics; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D000643:Ammonium Chloride; D000086:Acetazolamide