Effects of omeprazole and famotidine on (H+-K+) ATPase and acid secretion in rabbit gastric glands.

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Abstract
Effects of omeprazole, an anti-ulcer drug, on (H+-K+) ATPase activity and gastric acid secretion in a gastric mucosal gland preparation from rabbits were investigated. The mode of action of the substance was compared with famotidine, an H2 antagonist, by examining the effects of both drugs on the (H+-K+) ATPase of the rabbit gastric mucosa and on gastric acid secretion from the isolated rabbit gastric glands. Optimal assay conditions for (H+-K+) ATPase activity differed slightly from that reported for pig gastric mucosa, and they were pH 7.0, 2mM of MgCl2 and 50 mM of KCl. Omeprazole dose-dependently inhibited the enzyme activity with an IC50 of 4.2.mu.M, whereas famotidine was not inhibitory even at the highest concentration of 100.mu.M. Acid secretion in the glands was determined by measuring accumulation of 14C-aminopyrine. Omeprazole and famotidine showed almost the same inhibitory effect against histamine-stimulated gastric secretion, and their IC50 values were 0.35.mu.M. Omeprazole inhibited dibutyryl cyclic AMP-stimulated gastric acid secretion, but famotidine was not inhibitory even at the highest concentration of 100.mu.M. The reason for this difference was that (H+-K+) ATPase activity is linked to the final step of acid secretion. From these results, omeprazole can be expected to be useful for the treatment of peptic ulcer disease.