title: Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice.
abstract: OBJECTIVE
  Duodenal bicarbonate secretion is an important factor in epithelial protection. The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in acid-induced bicarbonate secretion is unknown. The aim of this study was to determine whether CFTR mediates acid-stimulated duodenal epithelial bicarbonate secretion.
  
  
  METHODS
  Basal and stimulated bicarbonate secretion was examined in the cystic fibrosis murine model cftrm1UNC, which displays defective CFTR in various organs including chloride transport abnormalities in epithelia. After anesthesia, the proximal duodenum was cannulated and perfused with isotonic saline, and [HCO3-] was determined.
  
  
  RESULTS
  Basal bicarbonate secretion was diminished in cystic fibrosis vs. normal mice, 2.8 +/- 0.7 vs. 4.7 +/- 1.7 mumol.cm-1.h-1, respectively (P < 0.001). Luminal acidification failed to elicit a bicarbonate secretory response in cystic fibrosis compared with normal littermates (peak response, 2.3 +/- 0.2 vs. 9.9 +/- 1.5 mumol.cm-1.h-1, respectively; P < 0.01). Prostaglandin E2- and vasoactive intestinal peptide-stimulated bicarbonate secretion were also significantly impaired in cystic fibrosis. Defective bicarbonate secretion in cystic fibrosis genotypes was due to decreased net fluid secretion and [HCO3-].
  
  
  CONCLUSIONS
  Basal and stimulated proximal duodenal bicarbonate secretion may involve a CFTR-mediated transport pathway. It is likely that CFTR, directly or indirectly, has a major functional role in mediating bicarbonate transport in the proximal duodenum.
authors.affiliation: Biomedical Laboratory, Odense University, Denmark. dhogan@ucsd.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Hogan
authors.forename: D L
authors.initials: DL
authors.lastname: Crombie
authors.forename: J I
authors.initials: JI
authors.lastname: Isenberg
authors.forename: P
authors.initials: P
authors.lastname: Svendsen
authors.forename: O B
authors.initials: OB
authors.lastname: Schaffalitzky de Muckadell
authors.forename: M A
authors.initials: MA
authors.lastname: Ainsworth
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000493:pharmacokinetics; D001693:Biological Transport, Active / Q000502:physiology; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D005838:Genotype; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014660:Vasoactive Intestinal Peptide; D015232:Dinoprostone; D006851:Hydrochloric Acid