REGULATION OF GASTRIC-ACID SECRETION BY HISTAMINE H-3 RECEPTORS IN THE DOG - AN INVESTIGATION INTO THE SITE OF ACTION

The involvement of histamine H-3 receptors in the regulation of gastri c acid secretion was investigated in the conscious dog with gastric fi stula, by the use of the selective agonist (R)alpha-methylhistamine an d the selective antagonist thioperamide. (R)alpha-methylhistamine (0.3 - 1.2 mu mol/kg/h) induced a dose-related inhibition of the acid secr etion induced by pentagastrin and by bombesin, maximum inhibition not exceeding 60-65%. The inhibitory effect of the H-3 agonist (0.6 mu mol /kg/h) was inhibitited by thioperamide (0.1 mu mol/kg/h), suggesting t hat the effect was entirely mediated by H, receptors. Thioperamide was also able to enhance the acid response to submaximal doses of pentaga strin and bombesin. The acid secretion induced by histamine was not mo dified by (R)alpha-methylhistamine (0.3 - 1.2 mu mol/kg/h) but it was significantly enhanced by thioperamide (0.1 mu mol/kg/h). Neither (R)a lpha-methylhistamine nor thioperamide significantly modified the incre ase in plasma gastrin levels induced by bombesin. In conclusion these data demonstrate that histamine H-3 receptors may represent an effecti ve mechanism for the negative control of stimulated gastric acid secre tion in the dog; however, since the inhibition was mainly evident agai nst stimuli which involve the release of histamine, a location of H-3 receptors in paracrine cells of the gastric mucosa rather than in gast rin producing cells or parietal cells seems more likely.