title: Metabolic acidosis in rats increases intestinal NHE2 and NHE3 expression and function.
abstract: Chronic metabolic acidosis increases intestinal Na absorption, although through undefined mechanisms. Whether this occurs through enhanced expression and/or function of the brush-border Na+/H+ exchangers (NHE)2 and NHE3 is unknown. Metabolic acidosis was induced in rats by feeding ammonium chloride through their drinking water. Intestinal NHE activities were measured using brush-border 22Na+ uptake. Western and Northern blots measured changes in protein and mRNA expression, respectively. Acidosis occurred within 2 days of ammonium chloride feedings but increased after 6 days. NHE2 and NHE3 activities, protein expression, and mRNA levels increased in acidotic rats compared with controls. In contrast, basolateral NHE1 expression was not affected. Brush-border alkaline phosphatase showed no effect of metabolic acidosis on cellular differentiation. This study demonstrated a direct effect of metabolic acidosis on NHE2 and NHE3 activity, expression, and gene transcription. Metabolic acidosis is one of the few circumstances shown to affect NHE2 function and expression, thus providing insights into the role of NHE2 on intestinal physiology.
authors.affiliation: Martin Boyer Laboratories, Inflammatory Bowel Disease Research Center, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lucioni
authors.forename: Christopher
authors.initials: C
authors.lastname: Womack
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.forename: Flavio L
authors.initials: FL
authors.lastname: Rocha
authors.forename: Cres
authors.initials: C
authors.lastname: Bookstein
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D007413:Intestinal Mucosa / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C513110:Slc9a2 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers