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-HT 1Dα receptors compared to 5-HT 1Dβ receptors, whereas, GR127935 ( N-[4-methoxy-3-(4-methyl-1-mpiperazinyl)phenyl]-2(methyl-4(-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide), a novel and selective 5-HT 1D receptor antagonist, has higher affinity for 5-HT 1Dβ receptors compared to 5-HT 1Dα 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 (pA 2 = 6.76) and GR127935 (apparent pA 2 = 9.4). In guinea-pig jugular vein, concentration-dependent relaxations evoked by sumatriptan were antagonised by ketanserin and GR127935 (apparent pA 2 = 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 (Ca 2+ channel blocker), eliminating the possibility that the inhibitory effects of ketanserin and GR127935 were due to the blockade of voltage-operated Ca 2+ channels. Thus, antagonism by ketanserin and GR127935 confirms the presence of 5-HT 1D 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-HT 1D receptors or the involvement of 5-HT 1Dα and 5-HT 1Dβ receptor subtypes.