Differences in the effects of ketanserin and GR127935 on 5-HT-receptor mediated responses in rabbit saphenous vein and guinea-pig jugular vein.
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.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007601:Jugular Veins / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011817:Rabbits; D012501:Saphenous Vein / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology
D010069:Oxadiazoles; D010879:Piperazines; D012702:Serotonin Antagonists; C090701:GR 127935; D012701:Serotonin; D018170:Sumatriptan; D007650:Ketanserin; D009543:Nifedipine