Kitazawa T, Shishido H, Sato T, Taneike T
Department of Pharmacology, Faculty of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
J Vet Pharmacol Ther. 1997 Jun;20(3):187-97. doi: 10.1111/j.1365-2885.1997.tb00094.x.
To clarify the role of histamine in uterine contractility, the effect of this biogenic amine on the myometrium of cyclic mature gilts was investigated by an isometric tension recording study in vitro. In addition, using crude membrane preparations isolated from the longitudinal (LM) and circular muscle (CM), the distribution of H1 histamine receptors was characterized by 3H-pyrilamine binding assay. Histamine caused a tetrodotoxin-resistant contractile response of LM and CM in Krebs solution, but LM (-logEC50 = 6.34) was more sensitive than CM (-logEC50 = 5.4). Pyrilamine decreased the excitatory response of histamine in both muscle layers. In pyrilamine-treated LM, a high concentration of histamine (1-30 microM) caused a slight inhibition of spontaneous contraction, and this inhibition was abolished by ranitidine. On the other hand, histamine did not cause any inhibition in the pyrilamine-treated CM preparations. Dimaprit (10-300 microM) concentration-dependently inhibited the spontaneous contraction of LM but not of CM. In the presence of pyrilamine and ranitidine, N alpha-methylhistamine, even at 10 microM, did not affect the spontaneous and electrical field stimulation (5Hz)-induced contraction of LM and CM layers. Specific 3H-pyrilamine binding sites were distributed heterogeneously in the swine myometrium. The maximum number of binding sites in LM (132.5 +/- 9.9 fmol/mg protein, n = 10) was 2.5 times higher than that in CM (52.2 +/- 3.2 fmol/mg protein, n = 6). These results indicate that there is a muscle layer-dependent difference of histamine-induced response in the swine myometrium. In the LM layer, histamine acts on both H1 and H2 histamine receptors, and causes contraction (via H1 receptors at a low concentration) or relaxation (via H2 receptors at a high concentration in the presence of pyrilamine). However, histamine causes only a contraction in the CM layer, likely the result of the absence of H2 histamine receptors. Histamine-induced contraction is conspicuous in the LM layer, because of the heterogeneous distribution of H1-receptors between LM and CM.
为阐明组胺在子宫收缩中的作用，通过体外等长张力记录研究，考察了这种生物胺对周期性成熟后备母猪子宫肌层的影响。此外，使用从纵肌（LM）和环肌（CM）分离的粗制膜制剂，通过3H-吡拉明结合试验对H1组胺受体的分布进行了表征。组胺在Krebs溶液中引起LM和CM的河豚毒素抗性收缩反应，但LM（-logEC50 = 6.34）比CM（-logEC50 = 5.4）更敏感。吡拉明降低了组胺在两个肌层中的兴奋反应。在吡拉明处理的LM中，高浓度的组胺（1 - 30 microM）引起自发收缩的轻微抑制，并且这种抑制被雷尼替丁消除。另一方面，组胺在吡拉明处理的CM制剂中未引起任何抑制。地马普利（10 - 300 microM）浓度依赖性地抑制LM的自发收缩，但不抑制CM的自发收缩。在吡拉明和雷尼替丁存在的情况下，即使在10 microM的浓度下，Nα-甲基组胺也不影响LM和CM层的自发收缩和电场刺激（5Hz）诱导的收缩。特异性3H-吡拉明结合位点在猪子宫肌层中分布不均一。LM中结合位点的最大数量（132.5 +/- 9.9 fmol/mg蛋白质，n = 10）比CM中（52.2 +/- 3.2 fmol/mg蛋白质，n = 6）高2.5倍。这些结果表明，猪子宫肌层中组胺诱导的反应存在肌层依赖性差异。在LM层中，组胺作用于H1和H2组胺受体，并引起收缩（在低浓度时通过H1受体）或舒张（在吡拉明存在下高浓度时通过H2受体）。然而，组胺仅在CM层中引起收缩，这可能是由于缺乏H2组胺受体所致。由于LM和CM之间H1受体的不均一分布，组胺诱导的收缩在LM层中较为明显。
