DUAL INHIBITORY PATHWAYS LINK ANTRAL SOMATOSTATIN AND HISTAMINE-SECRETION IN HUMAN, DOG, AND RAT STOMACH

Background & Aims: The secretion and function of antral histamine are not known. The aims of this study were to characterize the mechanisms of histamine release from the gastric antrum of humans, dogs, and rats and to determine whether histamine can influence thp secretion of som atostatin and gastrin. Methods: Somatostatin, gastrin, and histamine s ecretion from superfused antral segments was measured using radioimmun oassay. Results: Superfusion with thioperamide (H-3 antagonist) increa sed somatostatin and decreased gastrin and histamine secretion in all three species; superfusion with (r)-alpha-methylhistamine (H-3 agonist ) had the opposite effect. The pattern implied that endogenous histami ne, acting via H-3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion, which in turn regulates gastrin secretion. Superfusion with somatostatin antibody increased histamine secretion; the increase was not affected by the gastrin antagonist L-365,260, im plying that it was not mediated by the concurrent increase in gastrin but by suppression of an inhibitory pathway linking somatostatin and h istamine. Superfusion with methacholine alone and in the presence of e ither the H-3 agonist or antagonist confirmed the existence of recipro cal inhibitory pathways linking somatostatin and histamine. Conclusion s: Antral histamine in humans, dogs, and rats is linked to antral soma tostatin via reciprocal inhibitory paracrine pathways that serve to am plify the regulatory influence of somatostatin.