CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3- secretion

Background and aims: We investigated the role of the recently discovered, villous-expressed anion exchanger Slc26a6 (PAT1) and the predominantly crypt-expressed cystic fibrosis transmembrane regulator (CFTR) in basal and acid-stimulated murine duodenal HCO3- secretion in vivo, and the influence of blood HCO3- concentration on both. Methods: The proximal duodenum of anaesthetized mice was perfused in situ, and HCO3- secretion was determined by back-titration. Duodenal mucosal permeability was assessed by determining Cr-51-EDTA leakage from blood to lumen. Results: Compared with wild type (WT) littermates basal duodenal HCO3- secretory rates were slightly reduced in Slc26-deficient mice at low (similar to 21 mM), and markedly reduced at high blood HCO3- concentration (similar to 29 mM). In contrast, basal HCO3- secretion was markedly reduced in CFTR-deficient mice compared with WT littermates both at high and low blood HCO3- concentration. A short-term application of luminal acid increased duodenal HCO3- secretory rate in Slc26a6-deficient and WT mice to the same degree, but had no stimulatory effect in the absence of CFTR. Luminal acidification to pH 2.5 did not alter duodenal permeability. Conclusions: The involvement of Slc26a6 in basal HCO3- secretion in murine duodenum in vivo is critically dependent on the systemic acid/base status, and this transporter is not involved in acid-stimulated HCO3- secretion. The presence of CFTR is essential for basal and acid-induced HCO3- secretion irrespective of acid/base status. This suggests a coupled action of Slc26a6 with CFTR for murine basal duodenal HCO3- secretion, but not acid-stimulated secretion, in vivo.