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1 Department of Medicine, University of Cincinnati, Cincinnati, OH, USA
2 Department of Medicine, University of Cincinnati, Cincinnati, OH, USA; Veterans Affairs Medical Center at Cincinnati, Cincinnati, OH, USA
3 University of Tubingen, Tubingen, Germany
4 Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; Veterans Affairs Medical Center at West Side, Chicago, IL, USA
5 Department of Molecular Genetics, Biochemistry, and Microbiology, University of cincinnati, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: Manoocher.Soleimani{at}uc.edu.
The molecular identity of the apical bicarbonate-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 ~110-120 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. Based on its function and location we propose that AE4 may play an important role in mucosal protection.
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