title: CFTR and its key role in in vivo resting and luminal acid-induced duodenal HCO3- secretion.
abstract: OBJECTIVE
  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.
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors: A K
authors: AK
authors: Singh
authors: M
authors: M
authors: Sjöblom
authors: W
authors: W
authors: Zheng
authors: A
authors: A
authors: Krabbenhöft
authors: B
authors: B
authors: Riederer
authors: B
authors: B
authors: Rausch
authors: M P
authors: MP
authors: Manns
authors: M
authors: M
authors: Soleimani
authors: U
authors: U
authors: Seidler
mesh_terms: D000818:Animals; D017920:Antiporters / Q000172:deficiency / Q000502:physiology; D001639:Bicarbonates / Q000097:blood / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000502:physiology*; D004386:Duodenum / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D010539:Permeability; D000076988:Sulfate Transporters
chemical_list: D017920:Antiporters; D001639:Bicarbonates; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator