Razzaque Z, Longmore J, Hill R G
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Eur J Pharmacol. 1995 Sep 5;283(1-3):199-206. doi: 10.1016/0014-2999(95)00349-p.
Ketanserin has higher affinity for 5-HT1D alpha receptors compared to 5-HT1D beta receptors, whereas, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2(methyl-4(-(5-methyl- 1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide), a novel and selective 5-HT1D receptor antagonist, has higher affinity for 5-HT1D beta receptors compared to 5-HT1D alpha receptors. In the present study, we compared the effects of ketanserin and GR127935 on sumatriptan-induced responses of rabbit saphenous vein and guinea-pig jugular vein. In rabbit saphenous vein, contractile responses elicited by sumatriptan were antagonised by ketanserin (pA2 = 6.76) and GR127935 (apparent pA2 = 9.4). In guinea-pig jugular vein, concentration-dependent relaxations evoked by sumatriptan were antagonised by ketanserin and GR127935 (apparent pA2 = 5.9 and 10, respectively). Ketanserin but not GR127935, inhibited Ca(2+)-induced contraction of depolarised strips of guinea-pig ileum longitudinal muscle/myenteric plexus, however, in rabbit saphenous vein and guinea-pig jugular vein, 5-HT receptor mediated responses were insensitive to nifedipine (Ca2+ channel blocker), eliminating the possibility that the inhibitory effects of ketanserin and GR127935 were due to the blockade of voltage-operated Ca2+ channels. Thus, antagonism by ketanserin and GR127935 confirms the presence of 5-HT1D receptors in rabbit saphenous vein and guinea-pig jugular vein. The differential effects of ketanserin and GR127935 on responses elicited by sumatriptan in rabbit saphenous vein and guinea-pig jugular vein may reflect either species differences in 5-HT1D receptors or the involvement of 5-HT1D alpha and 5-HT1D beta receptor subtypes.
与5-HT1Dβ受体相比，酮色林对5-HT1Dα受体具有更高的亲和力，而新型选择性5-HT1D受体拮抗剂GR127935（N-[4-甲氧基-3-(4-甲基-1-哌嗪基)phenyl]-2(甲基-4(-(5-甲基-1,2,4-恶二唑-3-基)[1,1-联苯]-4-羧酰胺)与5-HT1Dα受体相比，对5-HT1Dβ受体具有更高的亲和力。在本研究中，我们比较了酮色林和GR127935对舒马曲坦诱导的兔隐静脉和豚鼠颈静脉反应的影响。在兔隐静脉中，舒马曲坦引起的收缩反应被酮色林（pA2 = 6.76）和GR127935（表观pA2 = 9.4）拮抗。在豚鼠颈静脉中，舒马曲坦引起的浓度依赖性舒张被酮色林和GR127935拮抗（表观pA2分别为5.9和10）。酮色林而非GR127935抑制了豚鼠回肠纵肌/肌间神经丛去极化条带的Ca(2+)诱导收缩，然而，在兔隐静脉和豚鼠颈静脉中，5-HT受体介导的反应对硝苯地平（Ca2+通道阻滞剂）不敏感，排除了酮色林和GR127935的抑制作用是由于电压门控Ca2+通道阻断的可能性。因此，酮色林和GR127935的拮抗作用证实了兔隐静脉和豚鼠颈静脉中存在5-HT1D受体。酮色林和GR127935对兔隐静脉和豚鼠颈静脉中舒马曲坦诱导的反应的不同影响可能反映了5-HT1D受体的种属差异或5-HT1Dα和5-HT1Dβ受体亚型的参与。
