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  • Title: CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3- secretion.
    Author: Singh AK, Sjöblom M, Zheng W, Krabbenhöft A, Riederer B, Rausch B, Manns MP, Soleimani M, Seidler U.
    Journal: Acta Physiol (Oxf); 2008 Aug; 193(4):357-65. PubMed ID: 18363901.
    Abstract:
    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 HCO(3)(-) secretion in vivo, and the influence of blood HCO(3)(-) concentration on both. METHODS: The proximal duodenum of anaesthetized mice was perfused in situ, and HCO(3)(-) secretion was determined by back-titration. Duodenal mucosal permeability was assessed by determining (51)Cr-EDTA leakage from blood to lumen. RESULTS: Compared with wild type (WT) littermates basal duodenal HCO(3)(-) secretory rates were slightly reduced in Slc26-deficient mice at low ( approximately 21 mm), and markedly reduced at high blood HCO(3)(-) concentration ( approximately 29 mm). In contrast, basal HCO(3)(-) secretion was markedly reduced in CFTR-deficient mice compared with WT littermates both at high and low blood HCO(3)(-) concentration. A short-term application of luminal acid increased duodenal HCO(3)(-) 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 HCO(3)(-) secretion in murine duodenum in vivo is critically dependent on the systemic acid/base status, and this transporter is not involved in acid-stimulated HCO(3)(-) secretion. The presence of CFTR is essential for basal and acid-induced HCO(3)(-) secretion irrespective of acid/base status. This suggests a coupled action of Slc26a6 with CFTR for murine basal duodenal HCO(3)(-) secretion, but not acid-stimulated secretion, in vivo.
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