The relationship between gastric acid secretion and gastric H+,K+-ATPase activity

The H+,K+-ATPase has been postulated to be the enzyme responsible for H+ secretion by the parietal cell. Omeprazole has been shown to be an inhibitor of acid secretion in vivo, but also in in vitro test models for acid secretion, including partly purified H+,K+-ATPase, the inhibitory action of omeprazole has been demonstrated (Wallmark, B., Jaresten, B. M., Larsson, H., Ryberg, B., Brändström, A., and Fellenius, E. (1983) Am. J. Physiol. 245, G64-G71). It was thus possible to use this compound to demonstrate a correlation between H+,K+-ATPase activity in rat oxyntic mucosa and in vivo H+ secretion. Two results were found. (a) Increasing oral doses of omeprazole progressively inhibited acid secretion, H+,K+-ATPase activity, and phosphoenzyme formation of a microsomal fraction isolated from the inhibited rat mucosa. Furthermore, a Mg2+-stimulated ATPase activity, associated with the H+,K+-ATPase membrane fraction, was not affected by the omeprazole treatment. (b) Recovery of H+,K+-ATPase activity following complete omeprazole inhibition was correlated with the appearance of acid secretion. The results indicate a strict relationship between the activity of the gastric H+,K+-ATPase in the microsomal fraction and gastric acid secretion.