Function and structure of parietal cells after H+-K+-ATPase blockade.

Omeprazole was administered to rabbits as a single dose or daily for 1 wk. H+-K+-ATPase and isolated gastric glands were prepared from the oxyntic corpus mucosa and used for functional and quantitative morphological studies. Both 10 and 100 mumol omeprazole/kg increased the pH of the gastric content when measured at death. The stimulated oxygen uptake and the rate of aminopyrine (AP) uptake were both inhibited in the isolated gastric gland preparations. Morphometric studies of biopsy specimens taken from the corpus mucosa and isolated gastric glands showed that omeprazole treatment increased the volume density of the acid compartments. This expansion provides an increased accumulation space for AP. Therefore, an increased AP uptake might be seen in glands isolated from omeprazole-treated animals. Blockade of the H2-receptor by ranitidine transformed the morphology of the cell into a more resting type and, furthermore, reduced the omeprazole-induced increase in the volume density of the acid compartments in the parietal cell. The H+-K+-ATPase activity measured in membrane fractions from the omeprazole-treated animals was decreased dose dependently and inhibited by 95% after 100 mumol omeprazole/kg. However, the concentration of the enzyme in these fractions did not change. These results indicate a specific inhibitory action of omeprazole on the H+-K+-ATPase.