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 ⁵¹Cr‐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 (∼21 mm), and markedly reduced at high blood HCO₃⁻ concentration (∼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.