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 microM) (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 microM), was partly depressed by 5-HT2-receptor antagonists in high concentrations (ketanserin 0.5 microM, LY53857, 1.0 microM), and was abolished by a non-selective antagonist of 5-HT1 and 5-HT2 receptors (methiothepin, 0.01 microM). 3. Amplifying potencies of agonists assessed by both Methods I and II were in the order 5-carbox-amidotryptamine (5-CT) greater than 5-HT greater than 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-HT,-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,-like receptors are distributed uniformly across the artery wall.
de la Lande
I S
IS
Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000737:chemistry*; D004431:Ear, External / Q000098:blood supply; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D011985:Receptors, Serotonin / Q000032:analysis* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D007650:Ketanserin; D008729:Methoxamine; D000109:Acetylcholine