Soldani G, Intorre L, Bertini S, Luchetti E, Coruzzi G, Bertaccini G
Laboratory of Veterinary Pharmacology, University of Pisa, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Aug;350(2):218-23. doi: 10.1007/BF00241100.
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)alpha-methylhistamine and the selective antagonist thioperamide. (R)alpha-methylhistamine (0.3-1.2 mumol/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 mumol/kg/h) was inhibited by thioperamide (0.1 mumol/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)alpha-methylhistamine (0.3-1.2 mumol/kg/h) but it was significantly enhanced by thioperamide (0.1 mumol/kg/h). Neither (R)alpha-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.
利用选择性激动剂（R）α-甲基组胺和选择性拮抗剂硫代哌啶，在有意识的胃瘘犬中研究了组胺H3受体在胃酸分泌调节中的作用。（R）α-甲基组胺（0.3 - 1.2 μmol/kg/h）诱导对五肽胃泌素和蛙皮素诱导的胃酸分泌产生剂量相关的抑制，最大抑制不超过60 - 65%。H3激动剂（0.6 μmol/kg/h）的抑制作用被硫代哌啶（0.1 μmol/kg/h）抑制，表明该作用完全由H3受体介导。硫代哌啶还能够增强对次最大剂量五肽胃泌素和蛙皮素的酸反应。组胺诱导的胃酸分泌未被（R）α-甲基组胺（0.3 - 1.2 μmol/kg/h）改变，但被硫代哌啶（0.1 μmol/kg/h）显著增强。（R）α-甲基组胺和硫代哌啶均未显著改变蛙皮素诱导的血浆胃泌素水平升高。总之，这些数据表明组胺H3受体可能是犬中刺激胃酸分泌负调控的一种有效机制；然而，由于抑制主要在涉及组胺释放的刺激中明显，H3受体位于胃黏膜旁分泌细胞而非胃泌素产生细胞或壁细胞似乎更有可能。
