Evidence for a 5-HT(1)-like receptor mediating the amplifying action of 5-HT in the rabbit ear artery.

1 The nature of the 5-hydroxytryptamine (5-HT) receptors which amplify the vasoconstrictor effect of methoxamine was examined in the rabbit isolated perfused ear artery with intact endothelium. Indices of amplification were leftward shifts of methoxamine dose-response (DR) curves produced by 5-HT (0.3 muM) (Method I), and the appearance of vasoconstrictor responses to 5-HT receptor agonists when methoxamine was present in a near-threshold concentration (Method II).2 The amplifying effect of 5-HT (Method I) was unaffected by prazosin (0.08 muM), was partly depressed by 5-HT(2)-receptor antagonists in high concentrations (ketanserin 0.5 muM, LY53857, 1.0 muM), and was abolished by a non-selective antagonist of 5-HT(1) and 5-HT(2) receptors (methiothepin, 0.01 muM).3 Amplifying potencies of agonists assessed by both Methods I and II were in the order 5-carboxamidotryptamine (5-CT)>5-HT>alpha-methyl 5-HT. The potency of sumatriptan (assessed by Method II only) was intermediate between those of 5-HT and alpha-methyl 5-HT.4 Ketanserin and LY53857 inhibited the amplifying action of 5-CT to about the same extent as that of 5-HT.5 The amplifying potencies of the agonists are in marked contrast to the reported contractile potencies in the rabbit aorta where the receptor is 5-HT(2), but are almost identical with reported contractile potencies in the dog saphenous vein where the receptor is 5-HT(1)-like.6 It is concluded that a 5-HT(1)-like receptor mediates the amplifying interaction between 5-HT and methoxamine in the rabbit ear artery which can be weakly blocked by ketanserin and LY53857.7 Since 5-CT was equipotent when applied separately to the intimal and adventitial surfaces of the artery, it is suggested that the 5-HT(1)-like receptors are distributed uniformly across the artery wall.