Differential effects of Na+, K(+)-ATPase inhibition by ouabain on acid secretory responses to histamine and bethanechol in the mouse isolated stomach.

1. The effect of Na+,K(+)-ATPase inhibition by ouabain on gastric acid secretion was studied in the mouse isolated whole stomach preparation. 2. Ouabain caused a transient enhancement of histamine-induced gastric acid secretion followed by an inhibitory phase. On the other hand, ouabain caused a rapid reduction of bethanechol-stimulated acid secretion without an enhancement phase. 3. In dibutyryl cyclic AMP-induced acid secretion, ouabain led to a transient increase in acid secretion followed by a fall, as was seen with the histamine stimulation. Ouabain caused a rapid reduction of A23187-induced acid secretion. 4. Ouabain by itself increased basal acid secretion, and thereafter slowly suppressed the acid secretion. 5. Atropine inhibited both the ouabain-induced enhancement of the stimulated gastric acid secretion and the ouabain-induced stimulation of basal acid secretion. 6. The present study showed that Na+,K(+)-ATPase inhibition by ouabain caused a phasic enhancement of the stimulated gastric acid secretion through release of endogenous acetylcholine when the secretagogues act via an intracellular cyclic AMP pathway. It also inhibited the stimulated acid secretion irrespective of secretagogues, probably through its inhibitory effect on Na+,K(+)-ATPase in the gastric parietal cell.