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MUCOSAL BIOLOGY

Identification of an apical Cl^-/HCO₃^- exchanger in gastric surface mucous and duodenal villus cells

Departments of ¹Medicine and ⁶Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati 45267; ²Veterans Affairs Medical Center, Cincinnati, Ohio 45220; ³University of Tubingen, D-72076 Tubingen, Germany; and ⁴Department of Medicine, University of Illinois at Chicago, and ⁵Veterans Affairs Medical Center at West Side, Chicago, Illinois 60612

Submitted 22 May 2003 ; accepted in final form 28 July 2003

The molecular identity of the apical HCO₃^--secreting transporter in gastric mucous cells remains unknown despite its essential role in preventing injury and ulcer by gastric acid. Here we report the identification of a Cl^-/HCO₃^- exchanger that is located on apical membranes of gastric surface epithelial cells. RT-PCR studies of mouse gastrointestinal tract mRNAs demonstrated that this transporter, known as anion exchanger isoform 4 (AE4), is expressed in both stomach and duodenum. Northern blot analysis of RNA from purified stomach epithelial cells indicated that AE4 is expressed at higher levels in mucous cells than in parietal cells. Immunoblotting experiments identified AE4 as a 110- to 120-kDa protein in membranes from stomach epithelium and apical membranes from duodenum. Immunocytochemical staining demonstrated that AE4 is expressed in apical membranes of surface cells in both mouse and rabbit stomach and duodenum. Functional studies in oocytes indicated that AE4 functions as a Cl^-/HCO₃^- exchanger. These data show that AE4 is an apical Cl^-/HCO₃^- exchanger in gastric mucous cells and duodenal villus cells. On the basis of its function and location, we propose that AE4 may play an important role in mucosal protection.

anion exchanger isoform 4; chloride/bicarbonate exchange; parietal cells; mucous cells; acid injury

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