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 somatostatin and gastrin. Methods: Somatostatin, gastrin, and histamine secretion from superfused antral segments was measured using radioimmunoassay. Results: Superfusion with thioperamide (H-3 antagonist) increased 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 histamine, 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, implying that it was not mediated by the concurrent increase in gastrin but by suppression of an inhibitory pathway linking somatostatin and histamine. Superfusion with methacholine alone and in the presence of either the H-3 agonist or antagonist confirmed the existence of reciprocal inhibitory pathways linking somatostatin and histamine. Conclusions: Antral histamine in humans, dogs, and rats is linked to antral somatostatin via reciprocal inhibitory paracrine pathways that serve to amplify the regulatory influence of somatostatin.