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REPORT
MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS
Departments of 1Medicine and 4Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio; 2Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; 3Department of Pathology, Children’s Hospital Medical Center, Cincinnati, Ohio; 5Department of Molecular and Cell Biology, University of California, Berkeley, California; and 6Veterans Affairs Medical Center, Cincinnati, Ohio
Submitted 26 January 2005 ; accepted in final form 23 March 2005
ABSTRACT
HCO3– secretion by gastric mucous cells is essential for protection against acidic injury and peptic ulcer. Herein we report the identification of an apical HCO3– transporter in gastric surface epithelial cells. Northern hybridization and RT-PCR demonstrate the expression of this transporter, also known as SLC26A9, in mouse and rat stomach and trachea (but not kidney). In situ hybridization in mouse stomach showed abundant expression of SLC26A9 in surface epithelial cells with apical localization on immunofluorescence labeling. Functional studies in HEK-293 cells demonstrated that SLC26A9 mediates Cl–/HCO3– exchange and is also capable of Cl–-independent HCO3– extrusion. Unlike other anion exchangers or transport proteins reported to date, SLC26A9 activity is inhibited by ammonium (NH4+). The inhibitory effect of NH4+ on gastric HCO3– secretion was also indicated by reduced gastric juxtamucosal pH (pHjm) in rat stomach in vivo. This report is the first to describe the inhibition of HCO3– transport in vitro and the reduction of pHjm in stomach in vivo by NH4+. Given its critical localization on the apical membrane of surface epithelial cells, its ability to transport HCO3–, and its inhibition by NH4+, we propose that SLC26A9 mediates HCO3– secretion in surface epithelial cells and is essential for protection against acidic injury in the stomach. Disease states that are associated with increased ammonia (NH3)/NH4+ generation (e.g., Helicobacter pylori) may impair gastric HCO3– secretion and therefore predispose patients to peptic ulcer by inhibiting SLC26A9.
anion exchange; gastric bicarbonate secretion; peptic ulcer
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