Present address: Division of Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3− secretion
Article first published online: 21 MAR 2008
© 2008 The Authors. Journal compilation © 2008 Scandinavian Physiological Society
Volume 193, Issue 4, pages 357–365, August 2008
How to Cite
Singh, A. K., Sjöblom, M., Zheng, W., Krabbenhöft, A., Riederer, B., Rausch, B., Manns, M. P., Soleimani, M. and Seidler, U. (2008), CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3− secretion. Acta Physiologica, 193: 357–365. doi: 10.1111/j.1748-1716.2008.01854.x
- Issue published online: 8 JUL 2008
- Article first published online: 21 MAR 2008
- Received 2 March 2008, revision requested 10 March 2008, revision received 12 March 2008, accepted 14 March 2008
- anion exchange;
- mucosal protection;
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.