Holmgren S, Grove D J, Nilsson S
Neuroscience. 1985 Feb;14(2):683-93. doi: 10.1016/0306-4522(85)90319-7.
The effect and mode of action of substance P was studied in a perfused stomach preparation and on isolated strip preparations of the stomach wall from the rainbow trout, Salmo gairdneri. Substance P was excitatory on the stomach muscle wall in a dose-dependent manner. Two other tachykinins, physalaemin and eledoisin, excited the preparations in a similar manner and in the same dose range. The effect of substance P was not antagonized by the substance P analogues [D-Pro2, D-Phe7, D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P (both 10(-5) M). Tetrodotoxin reduced or abolished the effect of substance P, while no reduction of the response was obtained after atropine, chlorisondamine or phentolamine (all 10(-6) M). 5-Hydroxytryptamine excited the stomach and this effect was not antagonized by tetrodotoxin, suggesting that the action of 5-hydroxytryptamine was direct on the smooth muscle. The 5-hydroxytryptamine antagonist methysergide, in a concentration which selectively blocked the response to 5-hydroxytryptamine, also blocked the response to substance P (10(-9)-10(-8) M). The outflow of 5-[3H]hydroxytryptamine from a preloaded perfused stomach was clearly increased by substance P, and this release was blocked by tetrodotoxin. Immunohistochemistry revealed the presence of nerve fibres and ganglion cells showing 5-hydroxytryptamine-like immunoreactivity in the myenteric plexus and smooth muscle layers of the stomach wall. The immunoreactive cells and nerve fibres were particularly abundant in the pyloric part of the stomach. It is concluded that the main effect of substance P on the stomach wall of the rainbow trout is indirect, via activation of a non-adrenergic, non-cholinergic neuron. The results are compatible with the view that this neuron exerts its action by release of 5-hydroxytryptamine. Supramaximal concentrations (greater than or equal to 10(-7) M) of substance P may in addition have a direct effect on the gastric smooth muscle.
在虹鳟鱼（Salmo gairdneri）的灌流胃标本以及离体胃壁条带标本上研究了P物质的作用及其作用方式。P物质对胃肌壁具有剂量依赖性兴奋作用。另外两种速激肽，即 Physalaemin 和 Eledoisin，在相似的剂量范围内以相似的方式兴奋标本。P物质的作用未被P物质类似物[D-Pro2, D-Phe7, D-Trp9]P物质和[D-Pro2, D-Trp7,9]P物质（均为10(-5) M）拮抗。河豚毒素降低或消除了P物质的作用，而在阿托品、氯异吲哚胺或酚妥拉明（均为10(-6) M）处理后反应未降低。5-羟色胺兴奋胃，且这种作用未被河豚毒素拮抗，提示5-羟色胺的作用是直接作用于平滑肌。5-羟色胺拮抗剂麦角新碱在选择性阻断对5-羟色胺反应的浓度下，也阻断了对P物质（10(-9)-10(-8) M）的反应。P物质可明显增加预先装载的灌流胃中5-[3H]羟色胺的流出，且这种释放被河豚毒素阻断。免疫组织化学显示，在胃壁的肌间神经丛和平滑肌层中存在显示5-羟色胺样免疫反应性的神经纤维和神经节细胞。免疫反应性细胞和神经纤维在胃的幽门部特别丰富。得出结论，P物质对虹鳟鱼胃壁的主要作用是间接的，通过激活非肾上腺素能、非胆碱能神经元。这些结果与该神经元通过释放5-羟色胺发挥作用的观点一致。P物质的超最大浓度（大于或等于10(-7) M）可能还对胃平滑肌有直接作用。
