Bado A, Moizo L, Laigneau J P, Lewin M J
Institut National de la Santé et de la Recherche Médicale, Unité 10, Hôpital Bichat, Paris, France.
Am J Physiol. 1992 Jan;262(1 Pt 1):G56-61. doi: 10.1152/ajpgi.1992.262.1.G56.
The effects of the specific H3 agonist (R)-alpha-methylhistamine (alpha-MeHA) and the specific H3 antagonist thioperamide were examined on histamine release and acid secretion [( 14C]-aminopyrine (AP) accumulation) by isolated rabbit gastric glands. Thioperamide significantly enhanced basal histamine release from the glands (+50% at 30 min for 10(-7) M thioperamide; P less than 0.01), and this increase was prevented by alpha-MeHA. Histamine-elicited AP accumulation was increased by 18% (P less than 0.05) by 10(-7) M thioperamide and decreased by 70% (P less than 0.01) by 10(-6) M of the H2 antagonist ranitidine. Thioperamide alone significantly enhanced AP accumulation in a dose-dependent manner, whereas alpha-MeHA had no effect of its own on this accumulation. Thioperamide stimulation of basal AP accumulation was not modified by ranitidine but was 50% decreased by alpha-MeHA. Furthermore, carbachol-induced AP accumulation was decreased by alpha-MeHA and increased by thioperamide; the latter effect was not blocked by ranitidine. These findings support that H3 receptors pharmacologically distinct from H2 receptors are involved in the regulation of histamine-stimulated acid secretion. They further suggest that these gastric H3 receptors occur in the gastric glands as 1) H3 autoreceptors located on the histamine-secreting cells and acting to downregulate histamine release from these cells and 2) H3 (or H3-like) receptors located on the parietal cell and regulating in a negative manner the acid secretory process.
研究了特异性H3激动剂（R）-α-甲基组胺（α-MeHA）和特异性H3拮抗剂硫代哌啶对分离的兔胃腺组胺释放和酸分泌[（14C] -氨基比林（AP）蓄积）的影响。硫代哌啶显著增强了腺体的基础组胺释放（10^(-7) M硫代哌啶在30分钟时增加50%；P<0.01），而这种增加被α-MeHA阻断。10^(-7) M硫代哌啶使组胺诱导的AP蓄积增加18%（P<0.05），而10^(-6) M H2拮抗剂雷尼替丁使其减少70%（P<0.01）。单独使用硫代哌啶以剂量依赖性方式显著增强AP蓄积，而α-MeHA自身对这种蓄积没有影响。硫代哌啶对基础AP蓄积的刺激作用不受雷尼替丁影响，但被α-MeHA降低50%。此外，卡巴胆碱诱导的AP蓄积被α-MeHA降低，被硫代哌啶增加；后一种作用不被雷尼替丁阻断。这些发现支持与H2受体在药理学上不同的H3受体参与组胺刺激的酸分泌调节。它们进一步表明，这些胃H3受体存在于胃腺中，表现为：1）位于组胺分泌细胞上的H3自身受体，作用是下调这些细胞的组胺释放；2）位于壁细胞上的H3（或H3样）受体，以负向方式调节酸分泌过程。
