Soldani G, Mengozzi G, Intorre L, De Giorgi G, Coruzzi G, Bertaccini G
Laboratory of Pharmacology, University of Pisa, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Jan;347(1):61-5. doi: 10.1007/BF00168773.
The effect of (R)alpha-methylhistamine (MH) and thioperamide (selective agonist and antagonist respectively of histamine H3 receptors) was examined in conscious gastric fistula dogs to investigate the role of histamine H3 receptors in the control of basal and stimulated gastric acid secretion. Intravenous infusion of MH at 0.3 and 0.6 mumol/kg/h caused a significant reduction of the 2-deoxy-D-glucose (2-DG)-stimulated acid output, maximal inhibition being 60%. The inhibitory effect of MH was counteracted by thioperamide (0.1 mumol/kg/h), which, by itself, did not modify the 2-DG-induced acid secretion. The increase in plasma gastrin levels induced by 2-DG was not significantly affected either by MH or by thioperamide. Under basal conditions MH (0.3 mumol/kg/h) did not induce any significant change in acid secretion and in plasma gastrin levels; by contrast, thioperamide (0.1 mumol/kg/h) produced a significant increase both in acid output and in plasma gastrin. These results suggest that activation of H3 receptors can exert a negative control in stimulated acid secretion in conscious dogs, when cholinergic pathways to acid secretion are activated by 2-DG; moreover, the slight, but significant, stimulatory effect of thioperamide on basal acid output and basal plasma gastrin may be suggestive for a tonic inhibitory role of H3 receptors in the regulation of basal acid secretion, however, a nonspecific effect of this drug cannot be excluded.
在清醒的胃瘘犬中研究了（R）α-甲基组胺（MH）和硫代哌啶（分别为组胺H3受体的选择性激动剂和拮抗剂）的作用，以探讨组胺H3受体在基础胃酸分泌和刺激胃酸分泌控制中的作用。以0.3和0.6μmol/kg/h的速度静脉输注MH可使2-脱氧-D-葡萄糖（2-DG）刺激的酸分泌显著减少，最大抑制率为60%。硫代哌啶（0.1μmol/kg/h）可抵消MH的抑制作用，而硫代哌啶本身并不改变2-DG诱导的酸分泌。2-DG诱导的血浆胃泌素水平升高不受MH或硫代哌啶的显著影响。在基础条件下，MH（0.3μmol/kg/h）不会引起酸分泌和血浆胃泌素水平的任何显著变化；相比之下，硫代哌啶（0.1μmol/kg/h）可使酸分泌和血浆胃泌素均显著增加。这些结果表明，当2-DG激活酸分泌的胆碱能途径时，H3受体的激活可对清醒犬的刺激酸分泌发挥负性控制作用；此外，硫代哌啶对基础酸分泌和基础血浆胃泌素的轻微但显著的刺激作用可能提示H3受体在基础酸分泌调节中具有紧张性抑制作用，然而，不能排除该药物的非特异性作用。
