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REPORT

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl^–/HCO₃^– exchange, and is inhibited by NH₄⁺

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 (pH_jm) in rat stomach in vivo. This report is the first to describe the inhibition of HCO₃^– transport in vitro and the reduction of pH_jm 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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