INHIBITING GASTRIC H-K+-ATPASE ACTIVITY BY OMEPRAZOLE PROMOTES DEGENERATION AND PRODUCTION OF PARIETAL-CELLS()

Parietal cell morphology was studied after chronic inhibition of gastr ic H+-K+-adenosinetriphosphatase (ATPase) by omeprazole. Gastric mucos a from rabbits treated with omeprazole every 12 h (1 mg/kg sc) for 5 d ays were compared with sham-injected animals using immunohistochemistr y and electron microscopy. Three immunocytochemical markers, including antibodies against the alpha- and beta-subunits of the H+-K+-ATPase, showed that some parietal cells in omeprazole-treated rabbits displaye d light areas and granularity in their cytoplasm. These abnormalities were also apparent in semithin sections. Electron microscopy was used to categorize and quantitate the specific structural abnormalities in parietal cells. Cells were classified as normal, altered, or degenerat ed. For control tissues, altered and degenerated parietal cells were f ew; they collectively represented 6% of total parietal cells and were located mainly deep in the gland base. For omeprazole-treated tissues, altered and degenerated parietal cells occurred throughout the gland and averaged 62% of total parietal cells. In addition, macrophages inv aded the mucosa presumably to eliminate degenerated cells. Although th ere was an increase in parietal cell degeneration, enhanced parietal c ell generation was suggested by increases in mitosis among proliferati ve cells and, more specifically, in the number of preparietal cells. A fter 3 days of recovery from the omeprazole regimen, parietal cells an d the gastric mucosa appeared to recover the normal morphology. In con clusion, blocking H+-K+-ATPase by omeprazole enhances degeneration and macrophage-mediated elimination of parietal cells and also causes an increase in preparietal cell production. Thus omeprazole temporarily c hanges the dynamic features of parietal cells in the rabbit to make th em die early and grow fast.