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Am J Physiol Cell Physiol (April 21, 2004). doi:10.1152/ajpcell.00474.2003
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Submitted on October 31, 2003
Accepted on April 14, 2004

Three Distinct Mechanisms of HCO3 Secretion in Rat Distal Colon

Sadasivan Vidyasagar1, Vazhaikkurichi M Rajendran1*, and Henry J Binder1

1 Internal Medicine, Yale University, New Haven, CT, USA

* To whom correspondence should be addressed. E-mail: vazhaikkurichi.rajendran{at}yale.edu.

HCO3 secretion has been long recognized in the mammalian colon but has not been well characterized. Although most studies of colonic HCO3 secretion revealed evidence of lumen Cl dependence suggesting a role for an apical membrane Cl-HCO3 exchange, direct examination of HCO3 secretion in isolated crypt from rat distal colon did not identify Cl-dependent HCO3 secretion but found that cAMP induced Cl-independent HCO3 secretion. Studies were, therefore, initiated to determine the characteristics of HCO3 secretion in isolated colonic mucosa which will identify HCO3 secretion in both surface and crypt cells. HCO3 secretion was measured in rat distal colonic mucosa stripped of muscular and serosal layers using pH stat technique. Basal HCO3 secretion (5.6 ± 0.03 µEq/h.cm2) was abolished by removal of either lumen Cl or bath HCO3; this Cl-dependent HCO3 secretion was also inhibited by 100 µM DIDS (0.5 ± 0.03 µEq/h.cm2), but not by NPPB, a Cl channel blocker. 8 Br-cAMP induced Cl-independent HCO3 secretion (as well as inhibiting Cl-dependent HCO3 secretion) which was inhibited by NPPB and glibenclamide, a CFTR blocker, but not by DIDS. Iso-butyrate, a poorly metabolized SCFA, also induced Cl-independent, DIDS-insensitive, saturable HCO3 secretion which was not inhibited by NPPB. Three distinct and separate HCO3 secretory mechanisms were identified: a) Cl-dependent that is associated with apical membrane Cl-HCO3 exchange; b) cAMP-induced that is a result of an apical membrane anion channel; and c) SCFA-dependent that is associated with an apical membrane SCFA-HCO3 exchange.




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