Stimulation of adenylate cyclase of guinea pig gastric mucosa by histamine, sodium fluoride and 5'-guanylylimidodiphosphate and inhibition by histamine H1- and H2-receptor antagonists in vitro

Abstract

There are experimental data indicating that cyclic AMP is involved in the regulation of gastric acid secretion in various mammalian species. In a broken cell preparation of guinea pig gastric mucosa the effects of some stimulants of gastric acid secretion on the activity of adenylate cyclase were studied. The basal adenylate cyclase activity was 483 +/- 43 pmoles cyclic AMP/mg protein x 10 min. The activity could be stimulated by histamine maximally 5-fold, by sodium fluoride (NaF) maximally 20-fold and by 5-guanylylimidodiphosphate (GMP-PNP) maximally 10-fold. Neither pentagastrin nor carbachol were able to stimulate the adenylate cyclase. Stimulants of adrenergic alpha- or beta-receptors (phenylephrine, isoproterenol) were also ineffective. The activation of the adenylate cyclase by histamine was inhibited by the histamine H1-receptor antagonists diphenhydramine and mepyramine as well as by the histamine H2-receptor antagonist metiamide. On the other hand, the stimulatory action of NaF OR GMP-PNP could be antagonized only by high concentrations of dipenhydramine or mepyramine while metiamide showed no antagonizing effect in this respect. Thus this preparation can be used as a tool to determine the activity and specificity of histamine H2-receptor antagonists.