Expression and cell-specific and membrane-specific localization of NHE-3 in the human and guinea pig upper...

Na+/H+ exchangers (NHEs) are vital transmembrane transport proteins mediating the electroneutral exchange of Na+ and H+ ions in mammalian cells. In the epithelium of the lower intestine, the isoform NHE-3 is apparently involved in Na+ absorption; however, its presence and cellular localization in the duodenum and particularly in the stomach remain largely unclear. Therefore, we studied the human and guinea pig stomach and duodenum for the expression, regional and mucosal distribution pattern, and membrane-specific localization of NHE-3. Reverse transcription/polymerase chain reaction analyses revealed strong expression of NHE-3 in the stomach and duodenum, where it was identified as a 85-kDa immunoreactive protein by Western blotting experiments. Whereas NHE-3 was localized to the basolateral membrane of surface mucous cells of the stomach, it was exclusively confined to the brush border membrane of epithelial cells in the duodenum. We conclude that the basolateral NHE-3 in the stomach protects the mucosa by secreting protons that diffuse into the mucous cells. In the duodenum, the localization of NHE-3 to the apical membrane of enterocytes suggests a resorptive function by directional Na+ transport. These findings indicate that NHE-3 may be involved in various segment-specific functions in the upper gastrointestinal tract.