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1 Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; Department of Internal Medicine I, University of Tubingen, Tubingen, Germany
2 Department of Internal Medicine I, University of Tubingen, Tubingen, Germany
3 Department of Anatomy I, Hannover Medical School, Hannover, Germany
4 Department of Molecular Genetics, University of Cincinnati, Cincinnati, OH, USA
5 Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
* To whom correspondence should be addressed. E-mail: seidler.ursula{at}mh-hannover.de.
The Na+/H+ exchanger isoform NHE2 is highly expressed in the intestinal tract, but its physiological role has remained obscure. The aim of this study was to define its expression, location, and regulatory properties in murine colon, and to look for the compensatory changes in NHE2 (-/-) colon that allow normal histology and absorptive function. To this end, we measured murine proximal colonic surface and crypt cell NHE1-3 expression levels, transport rates in response to acid, hyperosmolarity and cAMP in murine proximal colonic crypts, as well as changes in transcript levels and acid-activated NHE activity in NHE2 (-/-) crypts. We found that NHE2 was expressed most abundantly in crypts, NHE1 equally in crypts and surface cells, and NHE3 much stronger in surface cells. NHE2, like NHE1, was activated by low pHi, hyperosmolarity, and cAMP, whereas NHE3 was activated only by low pHi. Crypts isolated from NHE2 (-/-) mice displayed increased acid-activated NHE1- and NHE3-attributable Na+/H+ exchange activity, no change in NHE1 expression, and NHE3 expression levels twice as high as in normal littermates. No change in cellular ultrastructure was found in NHE2 (-/-) colon. Our results demonstrate high NHE2 expression in the crypts and suggest a role for NHE2 in cryptal pHi and volume homeostasis.
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