Backround: 

Recent investigations have revealed the expression of a multitude of basolateral acid/base transporters in gastric parietal cells, but the physiological significance of many of them is not established.

Aim and Methods: 

The study was designed to elucidate the physiological role of the Na⁺/HCO₃^- cotransporter pNBC1, the Na⁺/H⁺ exchangers NHE1 and NHE2, all abundantly expressed in parietal cells. Isolated gastric mucosae from ten days old mice (as both NBC1- and NHE1-deficient mice have a short life expectancy) were placed in classical Ussing chambers and basal and forskolin-stimulated acid secretory rate determined by back titration. Identical experiments were performed with selective pharmacological inhibitors of NBC and NHEs. Parietal cell ultrastructure was examined by electron microscopy, expression of H⁺/K⁺- ATPase was assessed by quantitative RT-PCR and immunohistochemistry, epitheial cell apoptosis assessed by the TUNEL assay, and proliferation by immunohistochemistry with anti-Ki67, anti-histone.

Results: 

Forskolin-stimulated acid secretion was significantly reduced (by >50%) in NBC1-deficient gastric mucosa, or after pharmacological inhibition of NBC1, but remained unaltered in NHE1- or Slc26a7 deficient gastric mucosa in ten days old mice, or after pharmacological inhibition of NHE1 and NHE2. Parietal cell number, ultrastructure, H⁺/K⁺-ATPase expression and epithelial cell proliferation were normal in NBC1- as well as NHE1 deficient mice. This indicates that pNBC1 likely serves as an additional base extrusion pathway in addition to the Cl^-/HCO₃^- exchanger AE2. In contrast, NHE2-deficient mucosae secreted acid only as a short "burst, and displayed a reduction of H⁺/K⁺-ATPase but not AE2 expression. At postnatal day 10, no difference in apoptotic rate, proliferative indices, histology, and parietal cell numbers were detected in NHE2 +/+ and -/- mice, whereas a complete change of the gastric proliferative zone and marked loss of parietal cell number was seen in adult stomach.