Blocking of histamine H2 receptors enhances parietal cell degeneration in the mouse stomach

The effects of the histamine H2 receptor antagonist, ranitidine, on parietal cell lineage was studied in the mouse stomach by using light and electron microscopy techniques. Mice were continuously infused for 15, 30, and 42 hr with ranitidine. Semithin sections examined under the light microscope revealed spherical light areas in the cytoplasm of parietal cells which in thin sections under the electron microscope appeared to be vacuoles. Cells were categorized as normal, altered and damaged. While altered cells were characterized by dilated canaliculi and vacuoles, the damaged cells showed signs of necrosis or apoptosis. In control mice, altered and damaged parietal cells were consistently few and only found in the pit or base regions of the epithelial units. After 15-hr-treatment with ranitidine, 40% of the parietal cells were altered. After 30 hr infusion, altered parietal cells became 53% of the examined population, and after 42 hr, 72% of the parietal cells were affected (42% altered and 30%, damaged). The gradual increase in parietal cell vacuolation was associated with an increase in the census of pre-parietal cells. Some mice were allowed to recover from treatment for 4 days. The appearance of normal parietal cells and disappearance of damaged cells was observed and the gastric glands became morphologically normal. In conclusion, inhibiting acid secretion by blocking the histamine H2 receptors, enhanced not only the degenerative elimination of parietal cells but also the production of pre-parietal cells and thus, the recovery of the population was prompt.