SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+ (Report)

• Published in: American Journal of Physiology: Cell Physiology Vol. 289; no. 2; pp. C493 - C505
• Main Authors: Xu, Jie, Henriksnas, Johanna, Barone, Sharon, Witte, David, Shull, Gary E, Forte, John G, Holm, Lena, Soleimani, Manoocher
• Format: Journal Article
• Language: English
• Published: United States 01.08.2005
• Subjects: Animals; Blotting, Northern; Blotting, Western; Chloride-Bicarbonate Antiporters - genetics; Chloride-Bicarbonate Antiporters - metabolism; Chloride-Bicarbonate Antiporters/genetics/metabolism; Cloning, Molecular; Electrophoresis, Polyacrylamide Gel; Epithelial Cells - metabolism; Fluorescent Antibody Technique; Gastric Mucosa - metabolism; Humans; In Situ Hybridization; Mice; Quaternary Ammonium Compounds - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Research Support; N.I.H; RNA; Cloning; U.S. Gov't; Messenger/analysis; Blotting; Molecular; Extramural; Western; P.H.S; Polyacrylamide Gel; Northern; Electrophoresis; Non-U.S. Gov't
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00030.2005

Departments of 1 Medicine and 4 Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio; 2 Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; 3 Department of Pathology, Children’s Hospital Medical Center, Cincinnati, Ohio; 5 Department of Molecular and Cell Biology, University of California, Berkeley, California; and 6 Veterans Affairs Medical Center, Cincinnati, Ohio Submitted 26 January 2005 ; accepted in final form 23 March 2005 ABSTRACT HCO 3 – secretion by gastric mucous cells is essential for protection against acidic injury and peptic ulcer. Herein we report the identification of an apical HCO 3 – 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 – /HCO 3 – exchange and is also capable of Cl – -independent HCO 3 – extrusion. Unlike other anion exchangers or transport proteins reported to date, SLC26A9 activity is inhibited by ammonium (NH 4 + ). The inhibitory effect of NH 4 + on gastric HCO 3 – 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 HCO 3 – transport in vitro and the reduction of pH jm in stomach in vivo by NH 4 + . Given its critical localization on the apical membrane of surface epithelial cells, its ability to transport HCO 3 – , and its inhibition by NH 4 + , we propose that SLC26A9 mediates HCO 3 – secretion in surface epithelial cells and is essential for protection against acidic injury in the stomach. Disease states that are associated with increased ammonia (NH 3 )/NH 4 + generation (e.g., Helicobacter pylori ) may impair gastric HCO 3 – secretion and therefore predispose patients to peptic ulcer by inhibiting SLC26A9. anion exchange; gastric bicarbonate secretion; peptic ulcer Address for reprint requests and other correspondence: M. Soleimani, Division of Nephrology and Hypertension, Dept. of Medicine, Univ. of Cincinnati, 231 Albert Sabin Way, MSB G259, Cincinnati, OH 45267-0585 (e-mail: Manoocher.Soleimani{at}uc.edu )