Sinanović O, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Eur J Pharmacol. 1987 Nov 17;143(3):353-60. doi: 10.1016/0014-2999(87)90459-6.
The mechanism of the vasoconstriction caused by 5-HT was analysed pharmacologically in isolated, perfused skeletal muscle branches of the canine femoral artery. An intraluminal injection of serotonin (5-HT) produced a marked vasoconstriction and the dose-response curve was bell-shaped. The 5-HT-induced response was inhibited by methysergide and ketanserin but a larger dose of ketanserin (10-30 micrograms) reduced the maximal responses to 5-HT, indicating its general depressant action. Norepinephrine (NE) and KCl-induced constrictions were not significantly affected by methysergide. Ketanserin significantly suppressed the NE-induced response at a relatively large dose but not the KCl-induced one. 5-HT- and KCl-induced constrictions were not modified by a potent alpha 1-adrenoceptor antagonist, bunazosin. It is considered that 5-HT may mediate its contractile effect on these arteries via specific 5-HT2 receptors but not alpha-adrenoceptors. Diltiazem at a relatively large dose (30-100 micrograms) slightly but significantly depressed NE-induced constrictions, and KCl-induced responses were markedly depressed by diltiazem (10-100 micrograms). On the other hand, 5-HT-induced constrictions were not suppressed by diltiazem at any of the doses used. It was shown that cold storage (at 4 degrees C, for 3-7 days) did not significantly modify 5-HT-induced responses although the KCl-induced effects were suppressed. Thus, it is considered that the calcium channel in these vessels may be dominantly depressed by cold storage. It is concluded that 5-HT-induced constriction in skeletal muscle arteries may be independent of the influx of extracellular Ca ions.
在犬股动脉分离灌注的骨骼肌分支中，从药理学角度分析了5-羟色胺（5-HT）引起血管收缩的机制。腔内注射5-羟色胺（5-HT）可产生明显的血管收缩，剂量-反应曲线呈钟形。5-HT诱导的反应可被麦角新碱和酮色林抑制，但较大剂量的酮色林（10 - 30微克）可将对5-HT的最大反应降低，表明其具有普遍的抑制作用。麦角新碱对去甲肾上腺素（NE）和氯化钾诱导的血管收缩无明显影响。酮色林在相对大剂量时可显著抑制NE诱导的反应，但对氯化钾诱导的反应无抑制作用。强效α1肾上腺素能受体拮抗剂布那唑嗪对5-HT和氯化钾诱导的血管收缩无影响。认为5-HT可能通过特定的5-HT2受体而非α肾上腺素能受体介导其对这些动脉的收缩作用。相对大剂量（30 - 100微克）的地尔硫䓬可轻微但显著地抑制NE诱导的血管收缩，地尔硫䓬（10 - 100微克）可显著抑制氯化钾诱导的反应。另一方面，在所用的任何剂量下，地尔硫䓬均未抑制5-HT诱导的血管收缩。结果表明，冷藏（4℃，3 - 7天）虽可抑制氯化钾诱导的效应，但对5-HT诱导的反应无明显影响。因此，认为冷藏可能主要抑制这些血管中的钙通道。结论是，5-HT诱导的骨骼肌动脉收缩可能与细胞外钙离子内流无关。
