RECIPROCAL INHIBITORY PARACRINE PATHWAYS LINK HISTAMINE AND SOMATOSTATIN SECRETION IN THE FUNDUS OF THE STOMACH

The present study was designed to examine the functional linkage betwe en histamine and somatostatin secretion in the fundus of the stomach. In segments of rat fundic mucosa, superfusion with thioperamide (H-3 a ntagonist) increased somatostatin and decreased histamine secretion; s uperfusion with (R)(-)-alpha-methylhistamine (H-3 agonist) had the opp osite effect, decreasing somatostatin and increasing histamine secreti on. The pattern implied that endogenous histamine, acting via H-3 rece ptors, exerts an inhibitory paracrine influence on somatostatin secret ion. Superfusion with somatostatin antibody (1:250)increased histamine secretion, implying that endogenous somatostatin, in turn, exerts an inhibitory paracrine influence an histamine secretion. Somatastatin an tibody also abolished the decrease in histamine secretion induced by t hioperamide and the increase:in histamine secretion induced by (R)(-)- alpha-methylhistamine, implying that changes in histamine secretion in duced by activation of H-3 receptors reflect changes in somatostatin s ecretion. Superfusion with the muscarinic agonist methacholine alone a nd in the presence of either H-3 agonist or H-3 antagonist confirmed t he existence of reciprocal inhibitory pathways Linking somatostatin an d histamine. We conclude that fundic histamine and somatostatin secret ion are linked via reciprocal inhibitory paracrine pathways that serve to amplify the regulatory influence of somatostatin.