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 ,2,4-oxadiazol-3-yl)[1,1-biph enyl]-4-carboxamide), a novel and selective 5-HT1D receptor antagonist , has higher affinity for 5-HT1D beta receptors compared to 5-HT1D alp ha receptors. In the present study, we compared the effects of ketanse rin and GR127935 on sumatriptan-induced responses of rabbit saphenous vein and guinea-pig jugular vein. In rabbit saphenous vein, contractil e 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, r espectively). Ketanserin but not GR127935, inhibited Ca2+-induced cont raction of depolarised strips of guinea-pig ileum longitudinal muscle/ myenteric plexus, however, in rabbit saphenous vein and guinea-pig jug ular vein, 5-HT receptor mediated responses were insensitive to nifedi pine (Ca2+ channel blocker), eliminating the possibility that the inhi bitory effects of ketanserin and GR127935 were due to the blockade of voltage-operated Ca2+ channels. Thus, antagonism by ketanserin and GR1 27935 confirms the presence of 5-HT1D receptors in rabbit saphenous ve in 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 differenc es in 5-HT1D receptors or the involvement of 5-HT1D alpha and 5-HT1D b eta receptor subtypes.