Involvement of the Anion Exchanger SLC26A6 in Prostaglandin E2- but not Forskolin-Stimulated Duodenal HCO3− Secretion

Background & Aims: SLC26A6 is a recently identified apical Cl−/HCO3− exchanger with strong expression in murine duodenum. The present study was designed to examine the role of SLC26A6 in prostaglandin E2 (PGE2)-, forskolin-, and carbachol-induced duodenal HCO3− secretion. Methods: Murine duodenal mucosal HCO3− secretion was examined in vitro in Ussing chambers and mucosal SLC26A6 expression levels were analyzed by semiquantitative reverse-transcription polymerase chain reaction. Results: Basal HCO3− secretion was diminished by 20%, PGE2-stimulated HCO3− secretory response by 59%, and carbachol-stimulated response was reduced by 35% in SLC26A6−/− compared with +/+ duodenal mucosa, whereas the forskolin-stimulated HCO3− secretory response was not different. In Cl−-free solutions, PGE2- and carbachol-stimulated HCO3− secretion was reduced by 81% and 44%, respectively, whereas forskolin-stimulated HCO3− secretion was not altered significantly. PGE2 and carbachol, but not forskolin, were able to elicit a Cl−-dependent HCO3− secretory response in the absence of short-circuit current changes in cystic fibrosis transmembrane conductance regulator knockout mice. Conclusions: In murine duodenum, PGE2-mediated HCO3− secretion is strongly SLC26A6 dependent and cystic fibrosis transmembrane conductance regulator independent, whereas forskolin-stimulated HCO3− secretion is completely SLC26A6 independent and cystic fibrosis transmembrane conductance regulator dependent. Carbachol-induced secretion is less pronounced, but occurs via both transport pathways. This suggests that PGE2 and forskolin activate distinct HCO3− transport pathways in the murine duodenum.