Morini G, Coruzzi G, Bertaccini G
Institute of Pharmacology, University of Parma, Italy.
Life Sci. 1997;60(25):PL377-82. doi: 10.1016/s0024-3205(97)00293-2.
The effect of the histamine H2 receptor agonist dimaprit on intestinal contractility was characterized on smooth muscle cells isolated from the longitudinal muscle of the guinea pig ileum. Dimaprit exerted two opposite effects on the contractility of isolated muscle cells: relaxation of cholecystokinin octapeptide (CCK-8)-induced contractions in the range of concentrations 10(-17)-10(-13) M and contraction at concentrations higher than 10(-13) M. The relaxant effect of dimaprit was totally prevented by the H2 blocker famotidine (10(-7) M), which, at the same time, enhanced the contractile effect of dimaprit, shifting to the left the concentration-response curve to the agonist. This contraction was not modified by the histamine H1 receptor antagonists pyrilamine and temelastine, tested both at 10(-7) M. By contrast, atropine 10(-8) M abolished the contractile effect of dimaprit, while leaving unchanged the response to CCK-8. Our results clearly indicate that longitudinal muscle cells of the guinea pig ileum possess inhibitory H2 receptors, which can be activated by very low concentrations of dimaprit; moreover, they revealed that dimaprit can have non-histaminergic effects, probably due to muscarinic receptor activation; however, concentrations about 10000 times higher than those necessary to activate H2 receptors, are required.
研究了组胺H2受体激动剂二甲双胍对从豚鼠回肠纵行肌分离的平滑肌细胞的肠收缩性的影响。二甲双胍对分离的肌细胞的收缩性产生两种相反的作用：在浓度范围为10（-17）-10（-13）M时松弛胆囊收缩素八肽（CCK-8）诱导的收缩，在浓度高于10（-13）M时收缩。二甲双胍的松弛作用完全被H2阻滞剂法莫替丁（10（-7）M）阻断，与此同时，法莫替丁增强了二甲双胍的收缩作用，使激动剂的浓度-反应曲线向左移动。在10（-7）M浓度下测试的组胺H1受体拮抗剂吡拉明和替美斯汀未改变这种收缩。相比之下，10（-8）M的阿托品消除了二甲双胍的收缩作用，而对CCK-8的反应保持不变。我们的结果清楚地表明，豚鼠回肠纵行肌细胞具有抑制性H2受体，其可被极低浓度的二甲双胍激活；此外，结果表明二甲双胍可能由于毒蕈碱受体激活而具有非组胺能作用；然而，所需浓度比激活H2受体所需浓度高约10000倍。
