Adenosine-3',5'-monophosphate: intracellular mediator for methyl xanthine stimulation of gastric secretion.

We postulated that methyl xanthines stimulate hydrochloric acid production in the isolated frog gastric mucosa by inhibiting the phosphodiesterase that destroys adenosine-3',5'-monophosphate (cyclic AMP). In support of this theory, several criteria were satisfied. Exogenously supplied cyclic AMP stimulated hydrogen and chloride transport in the spontaneously secreting mucosa and in the non-acid secreting mucosa in a similar fashion as did the methyl xanthines. Methyl xanthines increased the mucosal content of cyclic AMP, and the increase preceded the secretory response; thereafter, the magnitude of these two quantities paralleled each other. A correspondence was found between the concentration of methyl xanthines that affected acid secretion and the concentration of methyl xanthines that affected the tissue content of cyclic AMP. Theophylline was more effective than caffeine in increasing cyclic AMP content, which is in accord with the previously reported differences in their effect on acid secretion and phosphodiesterase activity.