Cyclic nucleotide response to acid-secreting stimuli in guinea pig gastric mucosa in vitro.

To investigate the mechanism of intracellular transmission of three representative stimuli for gastric acid secretion, the dose-response relations of cyclic nucleotides accompanied by acid secretion stimulated by histamine, pentagastrin and bethanechol were comparatively studied using an in vitro preparation of guinea pig gastric mucosa surviving with a constant potential difference and acid secretion sensitive to amytal. The following results were obtained. (1) Both histamine- and pentagastrin-stimulated acid secretion accompanied a significant increase in cyclic AMP contents in the gastric mucosa and in the serosal solution without any increase in cyclic GMP. However, the ratio of the increase in acid secretion to that in cAMP content was significantly greater with pentagastrin than with histamine, indicating that pentagastrin exerts its acid-secreting stimulus with less increase in cyclic AMP. (2) Stimulation with bethanechol resulted in a significant increase in the mucosal cyclic GMP content without any change in cyclic AMP. From these findings, it has been concluded that the above three stimuli were transmitted differently in the target cells, presenting evidence against the common final mediator theory of histamine for gastric acid secretion.