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Am J Physiol Gastrointest Liver Physiol (March 6, 2002). doi:10.1152/ajpgi.00529.2001
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Articles in PresS, published online ahead of print March 6, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00529.2001
Submitted on December 20, 2001
Accepted on February 6, 2002

Metabolic Acidosis in Rats Increases Intestinal NHE2 and NHE3 Expression and Function

Alvaro Lucioni1, Christopher Womack1, Mark W Musch1, Flavio G Rocha1, Cres Bookstein1, and Eugene B Chang1*

1 Department of Medicine, University of Chicago, Chicago, IL, USA

* To whom correspondence should be addressed. E-mail: mmusch{at}medicine.bsd.uchicago.edu.

Introduction: Chronic metabolic acidosis increases intestinal Na absorption, albeit through undefined mechanisms. Whether this occurs through enhanced expression and/or function of the brush border NHE2 and NHE3 is unknown. Methods: Metabolic acidosis was induced in rats by feeding ammonium chloride in 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. Results: Acidosis occurred within two days of ammonium chloride feedings, but increases after 6 days. NHE2 and NHE3 activities, protein expression and mRNA levels increased in acidotic rats compared to controls. In contrast, basolateral NHE1 expression was not affected. Brush border alkaline phosphatase showed no effect of metabolic acidosis on cellular differentiation. Conclusions: This study demonstrates a direct effect of metabolic acidosis on NHE2 and NHE3 activity, expression, and gene transcription. Metabolic acidosis is one of the few circumstances that have been shown to affect NHE2 function and expression, thus providing insights into the role of NHE2 on intestinal physiology.




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