EVIDENCE FOR A 5-HT1-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-mu-M) (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-mu-M), was partly depressed by 5-HT2-receptor antagonists in high concentrations (ketanserin 0.5-mu-M, LY53857, 1.0-mu-M), and was abolished by a non-selective antagonist of 5-HT1 and 5-HT2 receptors (methiothepin, 0.01-mu-M). 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-HT2, but are almost identical with reported contractile potencies in the dog saphenous vein where the receptor is 5-HT1-like. 6 It is concluded that a 5-HT1-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-HT1-like receptors are distributed uniformly across the artery wall.