Histamine, acting via H-3 receptors, inhibits somatostatin and stimulates acid secretion in isolated mouse stomach

Background & Aims: The role of histamine H-3, receptors in the regulation of gastric acid secretion is unclear. The present study was designed to characterize the location of H-3 receptors in the fundus of the stomach and the mechanism by which these receptors regulate acid secretion. Methods:Acid, somatostatin, and histamine secretions were measured in the isolated mouse stomach. Results: Thioperamide (H-3 antagonist) increased somatostatin and decreased histamine and acid secretion in a concentration-dependent manner. (r)-alpha-Methylhistamine (H-3 agonist) had the opposite effect, decreasing somatostatin and increasing histamine and acid secretion. The pattern implies that endogenous histamine, acting via H-3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion. Somatostatin antibody increased basal histamine secretion and abolished the decrease in histamine and acid secretion induced by thioperamide, confirming that changes in histamine and acid secretion induced by the activation of H-3 receptors reflected changes in somatostatin secretion. Similar effects were obtained when acid secretion was stimulated by histamine: thioperamide augmented somatostatin and thus inhibited acid secretion, and (r)-alpha-methylhistamine attenuated somatostatin and increased acid secretion. Conclusions: Reciprocal inhibitory paracrine pathways link histamine and somatostatin cells in the gastric fundus. Histamine, acting via H-3, receptors, augments acid secretion by eliminating the inhibitory influence of somatostatin.