Stimulation of formation of adenosine 3',5'-phosphate by histamine in myenteric ganglia isolated from guinea-pig small intestine

Effects of histamine and related agonists and antagonists on formation of cAMP were determined for enzymatically dissociated ganglia from the myenteric plexus of the guinea-pig small intestine. Formation of cAMP was stimulated by histamine in both dose- and time-dependent manners. The stimulatory action of histamine was suppressed by the histamine H₂ receptor antagonist, cimetidine. The histamine H₁ receptor antagonists, tripelennamine or pyrilamine also suppressed the stimulatory action of histamine, but only at concentrations 3-4 orders higher than required for cimetidine. Formation of cAMP was stimulated dose-dependently by the histamine H₂ receptor agonist, dimaprit. The histamine H₁ receptor agonist, 2-methyl-histamine, also stimulated cAMP production, but required a threshold concentration 4-5 orders higher than dimaprit. We conclude that histamine acts at the histamine H₂ receptor subtype to stimulate adenylate cyclase and the formation of cAMP in myenteric ganglia of the guinea-pig small bowel.