Involvement of the anion exchanger SLC26A6 in prostaglandin E2- but not forskolin-stimulated duodenal HCO3- secretion

Background & Aims: SILC26A6 is a recently identified apical Cl-/HCO3- exchanger with strong expression in murine duodenum. The present study was designed to examine the role of SILC26A6 in prostaglandin E-2 (PGE(2))(-), 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%, PGE(2)-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, PGE(2)- 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, PGE(2)-mediated HCO3- secretion is strongly SILC26A6 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-incluced 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.