Independence of apical Cl-/HCO3- exchange and anion conductance in duodenal HCO3- secretion

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 285; no. 5; p. G887
• Main Authors: Spiegel, S, Phillipper, M, Rossmann, H, Riederer, B, Gregor, M, Seidler, U
• Format: Journal Article
• Language: English
• Published: United States 01-11-2003
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Animals; Anions - metabolism; Bicarbonates - metabolism; Bumetanide - pharmacology; Cell Membrane - metabolism; Chloride-Bicarbonate Antiporters - metabolism; Chlorides - metabolism; Cyclic AMP - pharmacology; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Duodenum - metabolism; Electric Conductivity; Female; In Vitro Techniques; Ion Channels - physiology; Male; Mannitol - pharmacokinetics; Nitrobenzoates - pharmacology; Rabbits; Rats; Rats, Wistar; RNA, Messenger - metabolism; Sodium - metabolism
• ISSN: 0193-1857
• DOI: 10.1152/ajpgi.00083.2003

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.