Abstract
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 μM) (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 μM), was partly depressed by 5-HT2-receptor antagonists in high concentrations (ketanserin 0.5 μM, LY53857, 1.0 μM), and was abolished by a non-selective antagonist of 5-HT1 and 5-HT2 receptors (methiothepin, 0.01 μM).
3 Amplifying potencies of agonists assessed by both Methods I and II were in the order 5-carboxamidotryptamine (5-CT)>5-HT>α-methyl 5-HT. The potency of sumatriptan (assessed by Method II only) was intermediate between those of 5-HT and α-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.
Keywords: Rabbit ear artery, amplifying interactions, 5-hydroxytryptamine1-like receptors, 5-carboxamidotryptamine, sumatriptan
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Selected References
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