STIMULATION OF FORMATION OF ADENOSINE 3',5'-PHOSPHATE BY HISTAMINE INMYENTERIC 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 th e myenteric plexus of the guinea-pig small intestine. Formation of cAM P was stimulated by histamine in both dose- and time-dependent manners . The stimulatory action of histamine was suppressed by the histamine H-2 receptor antagonist, cimetidine. The histamine H-1 receptor antago nists, tripelennamine or pyrilamine also suppressed the stimulatory ac tion of histamine, but only at concentrations 3-4 orders higher than r equired for cimetidine. Formation of cAMP was stimulated dose-dependen tly by the histamine H-2 receptor agonist, dimaprit. The histamine H-1 receptor agonist, 2-methyl-histamine, also stimulated cAMP production , but required a threshold concentration 4-5 orders higher than dimapr it. We conclude that histamine acts at the histamine H-2 receptor subt ype to stimulate adenylate cyclase and the formation of cAMP in myente ric ganglia of the guinea-pig small bowel.