title: Bile deficiency induces changes in intestinal Cl(-) and HCO3 (-) secretions in mice.
abstract: OBJECTIVE
  Biliary tract obstruction is a common clinical lesion. However, the effect of biliary tract obstruction on intestinal secretion is poorly understood. In this study, we made an investigation on intestinal HCO3 (-) and Cl(-) secretions in an experimental model of murine biliary duct ligation.
  
  
  METHODS
  Murine intestinal mucosal HCO3 (-) and Cl(-) secretions were examined in vitro in Ussing chambers by pH-stat and short-circuit current (Isc ) techniques. The mRNA and protein expressions of the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+) -K(+) -2Cl(-) cotransporter (NKCC1) were analysed by real-time PCR, western blot and immunohistochemistry.
  
  
  RESULTS
  Basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with common biliary duct ligation were markedly elevated, compared with controls (P < 0.05 and P < 0.01). Further experiments showed that basal Cl(-) secretion and forskolin-stimulated duodenal and jejunal mucosal HCO3 (-) and Cl(-) secretions in mice with external bile drainage were also markedly elevated. CFTRinh -172 inhibited forskolin-stimulated HCO3 (-) and Cl(-) secretions. The mRNA and protein expression levels of CFTR and NKCC1 in the intestinal mucosa with both biliary duct ligation and external bile drainage were markedly higher than those in controls (P < 0.001). Bile acid administration restored the changes in function and expression of CFTR and NKCC1 in the intestinal mucosa.
  
  
  CONCLUSIONS
  Bile deficiency in the intestine up-regulates the expressions of intestinal mucosal CFTR and NKCC1 and enhances intestinal mucosal HCO3 (-) and Cl(-) secretion capacity, which contributes to the understanding of intestinal physiological function for patients with biliary duct obstruction.
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China; First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: P
authors.initials: P
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Hong
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Tuo
authors.forename: S
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015153:Blotting, Western; D002712:Chlorides / Q000378:metabolism*; D002779:Cholestasis / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D064506:Solute Carrier Family 12, Member 2 / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D001639:Bicarbonates; D002712:Chlorides; C578878:Slc12a2 protein, mouse; D064506:Solute Carrier Family 12, Member 2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Na+-K+-2Cl− cotransporter; bile; cystic fibrosis transmembrane conductance regulator; intestinal secretion