title: Independence of apical Cl-/HCO3- exchange and anion conductance in duodenal HCO3- secretion.
abstract: Reduced gastrointestinal HCO3- secretion contributes to malabsorption and obstructive syndromes in cystic fibrosis. The apical HCO3- transport pathways in these organs have not been defined. We therefore assessed the involvement of apical Cl-/HCO3- exchangers and anion conductances in basal and cAMP-stimulated duodenal HCO3- secretion. Muscle-stripped rat and rabbit proximal duodena were mounted in Ussing chambers, and electrical parameters, HCO3- secretion rates, and 36Cl-, 22Na+, and 3H+ mannitol fluxes were assessed. mRNA expression levels were measured by a quantitative PCR technique. Removal of Cl- from or addition of 1 mM DIDS to the luminal perfusate markedly decreased basal HCO3- secretion but did not influence the HCO3- secretory response to 8-bromo-cAMP, which was inhibited by luminal 5-nitro-2-(3-phenylpropylamino)-benzoate. Bidirectional 22Na+ and 36Cl- flux measurements demonstrated an inhibition rather than a stimulation of apical anion exchange during cAMP-stimulated HCO3- secretion. The ratio of Cl- to HCO3- in the anion secretory response was compatible with both Cl- and HCO3- being secreted via the CFTR anion channel. CFTR expression was very high in the duodenal mucosa of both species. We conclude that in rat and rabbit duodena, an apical Cl-/HCO3- exchanger mediates a significant part of basal HCO3- secretion but is not involved in the HCO3- secretory response to cAMP analogs. The inhibitor profile, the strong predominance of Cl- over HCO3- in the anion secretory response, and the high duodenal CFTR expression levels suggest that a major portion of cAMP-stimulated duodenal HCO3- secretion is directly mediated by CFTR.
authors.affiliation: Zentrum Innere Medizin, Abteilung IV, der Medizinischen Hochschule Hannover, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Spiegel
authors.forename: M
authors.initials: M
authors.lastname: Phillipper
authors.forename: H
authors.initials: H
authors.lastname: Rossmann
authors.forename: B
authors.initials: B
authors.lastname: Riederer
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: U
authors.initials: U
authors.lastname: Seidler
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004386:Duodenum / Q000378:metabolism*; D004553:Electric Conductivity; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D009579:Nitrobenzoates / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
chemical_list: D000838:Anions; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D007473:Ion Channels; D009579:Nitrobenzoates; D012333:RNA, Messenger; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D008353:Mannitol; D012964:Sodium; D000242:Cyclic AMP; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid