Background & Aims: Duodenal mucosal HCO3- secretion is a key factor in epithelial protection against gastric acid. We elucidated the role of apical chloride/base exchanger Slc26a6, and CFTR Cl- channel in murine duodenal HCO3- secretion in vivo.

Methods Basal, forskolin-, PGE2- and luminal acid-stimulated HCO3- secretion was examined in Slc26a6 and CFTR-deficient and WT mice. The isolated proximal duodenum was perfused in situ with isotonic saline, and HCO3- secretion was determined by back-titration. Results The basal secretory rates of bicarbonate were similar in Slc26a6-deficient and WT mice, but significantly reduced in mice deficient in CFTR. Luminal acidification induced the same increase in HCO3- secretion in Slc26a6-deficient and WT mice. Slc26a6-deficient mice displayed a significant reduction in HCO3- secretion in response to 10 mM luminal PGE2 compared to WT mice, while forskolin-stimulated HCO3- secretion was not different. CFTR-deficient mice displayed a substantial reduction in both PGE2-stimulated and acid-induced HCO3- secretion.

Conclusion Slc26a6 plays an important role in PGE2-stimulated murine duodenal HCO3- secretion in vivo. The HCO3- secretory response to acid, however, is not influenced by the lack of Slc26a6, whereas it is markedly decreased in the absence of CFTR.