Abstract
The involvement of histamine H3 receptors in the regulation of gastric acid secretion was investigated in the conscious dog with gastric fistula, by the use of the selective agonist (R)α-methylhistamine and the selective antagonist thioperamide. (R)α-methylhistamine (0.3–1.2 μmol/kg/h) induced a dose-related inhibition of the acid secretion induced by pentagastrin and by bombesin, maximum inhibition not exceeding 60–65%. The inhibitory effect of the H3 agonist (0.6 μmol/kg/h) was inhibitited by thioperamide (0.1 μmol/kg/h), suggesting that the effect was entirely mediated by H3 receptors. Thioperamide was also able to enhance the acid response to submaximal doses of pentagastrin and bombesin. The acid secretion induced by histamine was not modified by (R)a-methylhistamine (0.3–1.2 μmol/kg/h) but it was significantly enhanced by thioperamide (0.1 μmol/kg/h). Neither (R)α-methylhistamine nor thioperamide significantly modified the increase in plasma gastrin levels induced by bombesin. In conclusion these data demonstrate that histamine H3 receptors may represent an effective mechanism for the negative control of stimulated gastric acid secretion in the dog; however, since the inhibition was mainly evident against stimuli which involve the release of histamine, a location of H3 receptors in paracrine cells of the gastric mucosa rather than in gastrin producing cells or parietal cells seems more likely.
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Correspondence to: G. Bertaccini at the above address
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Soldani, G., Intorre, L., Bertini, S. et al. Regulation of gastric acid secretion by histamine H3 receptors in the dog: an investigation into the site of action. Naunyn-Schmiedeberg's Arch Pharmacol 350, 218–223 (1994). https://doi.org/10.1007/BF00241100
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DOI: https://doi.org/10.1007/BF00241100