Histamine and cAMP as possible mediators of acetylcholine-induced acid secretion.

Data are presented in support of the role of histamine and adenosine 3',5'-cyclic monophosphate (cAMP) as mediators of acetylcholine-induced acid secretion in frog gastric mucosa. These data also support the notion that acetylcholine-induced alkaline secretion is mediated by guanosine 3',5'-cyclic monophosphate (cGMP). Tissue cAMP and cGMP and rates of acid secretion and histamine release were measured in in vitro preparations of frog gastric mucosa that had been stimulated by acetylcholine. A transient increase in each variable was observed, the sequence of transient maxima being histamine release, cGMP, cAMP, and acid secretion. Atropine, an anticholnergic agent, eliminated all four transient increases, the variables remaining at resting levels. Metiamide, a H2-antagonist, modified the changes observed after acetylcholine stimulation. The acid secretion transience was abolished and the transient increase in tissue cAMP was greatly diminished, whereas the tissue of cGMP transience and histamine release transience remained unchanged. A model is proposed in which acetylcholine initiates two different processes, acid and alkaline secretions.