Centurión D, Sánchez-López A, De Vries P, Saxena P R, Villalón C M
Departamento de Farmacobiologia, CINVESTAV-IPN, Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México D.F., México.
Br J Pharmacol. 2001 Mar;132(5):991-8. doi: 10.1038/sj.bjp.0703913.
This study has further investigated the pharmacological profile of the GR127935-sensitive 5-HT(1) receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. One-minute intracarotid infusions of the agonists 5-hydroxytryptamine (5-HT; 0.1 - 10 microg min(-1); endogenous ligand) and sumatriptan (0.3 - 10 microg min(-1); 5-HT(1B/1D)), but not PNU-142633 (1 - 1000 microg min(-1); 5-HT(1D)) or LY344864 (1 - 1000 microg min(-1); 5-ht(1F)), produced dose-dependent decreases in internal carotid blood flow without changing blood pressure or heart rate. The responses to 5-HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 microg kg(-1); 5-HT(1B)), BRL15572 (300 microg kg(-1); 5-HT(1D)) or ritanserin (100 microg kg(-1); 5-HT(2)). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5-HT-induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin-treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5-HT-induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 microg min(-1)) the vasoconstrictor responses to 5-HT. Notably, in animals pretreated with 1000 microg kg(-1) of mesulergine, a 5-HT(2/7) receptor antagonist, 5-HT produced a dose-dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive. These results suggest that the GR127935-sensitive 5-HT(1) receptors mediating canine internal carotid vasoconstriction resemble the 5-HT(1B) but not the 5-HT(1D) or 5-ht(1F), receptor subtype.
本研究进一步探究了介导麻醉去迷走神经交感神经犬颈内动脉床血管收缩的GR127935敏感型5-羟色胺（5-HT）1受体的药理学特征。向颈内动脉内输注激动剂5-羟色胺（5-HT；0.1 - 10微克/分钟；内源性配体）和舒马曲坦（0.3 - 10微克/分钟；5-HT1B/1D）1分钟，可产生剂量依赖性的颈内动脉血流减少，而不改变血压或心率，但向颈内动脉内输注PNU-142633（1 - 1000微克/分钟；5-HT1D）或LY344864（1 - 1000微克/分钟；5-HT1F）则无此作用。5-HT引起的反应显然不受静脉注射拮抗剂SB224289（300微克/千克；5-HT1B）、BRL15572（300微克/千克；5-HT1D）或利坦色林（100微克/千克；5-HT2）的阻断。相反，舒马曲坦引起的反应可被SB224289拮抗，但不受BRL15572拮抗。在接受SB224289的动物中，但不是接受BRL15572的动物中，随后给予利坦色林可消除5-HT诱导的血管收缩，并揭示出血管舒张成分。同样，在利坦色林处理的动物中，随后给予SB224289，但不是BRL15572，可完全阻断5-HT诱导的血管收缩，显示出血管舒张。在最初接受BRL15572的动物中，随后给予SB224289对5-HT的血管收缩反应无影响（10微克/分钟时除外）。值得注意的是，在用1000微克/千克美舒麦角（一种5-HT2/7受体拮抗剂）预处理的动物中，5-HT产生剂量依赖性血管收缩反应，该反应几乎被SB224289消除。给予BRL15572后，未产生进一步的阻断作用，随后给予利坦色林也同样无活性。这些结果表明，介导犬颈内动脉血管收缩的GR127935敏感型5-HT1受体类似于5-HT1B，而不是5-HT1D或5-HT1F受体亚型。
