Summary
The effects of 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and sumatriptan were studied on endothelium-denuded rings of beagle dog large coronary arteries. Submicromolar concentrations of the compounds contracted the rings with the order of potency 5-CT > 5-HT >sumatriptan = methysergide. Concentrations greater than 2 μM of both 5-HT and 5-CT, and 60 μmol/l methysergide also caused concentration-dependent relaxation. Sumatriptan did not cause relaxation. Peak intrinsic activities relative to the plateau contraction to sumatriptan (1.00), were 5-CT 0.47, 5-HT 0.87 and methysergide 0.51. Ketanserin 1 μmol/l affected neither contractile responses nor relaxant responses to 5-CT, methysergide and sumatriptan and only caused marginal blockade of the contractile effects of 5-HT. Methiothepin 200 nM shifted the concentration-contractile response curves by around 2 log units, as expected from its affinity for 5-HT1-like receptors.
The rank order of contractile potency of the agonists, the antagonism by methiothepin and the resistance to blockade by ketanserin are consistent with a nearly exclusive involvement of 5-HT1-like receptors. Isolated large coronary arteries from beagle dogs may be a suitable model for the study of human coronary artery 5-HT1-like receptors that are involved in the spasm observed with 5-HT and sumatriptan.
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References
Blinks JR (1965) Convenient apparatus for recording contractions of isolated muscle. J Appl Physiol 20:775–777
Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576
Brazenor RM, Angus JA (1981) Ergometine contracts isolated canine coronary arteries by a serotonergic mechanism: No role for alpha adrenoceptors. J Pharmacol Exp Ther 218:530–536
Chester AH, Martin GR, Bodelsson M, Arneklo-Nobin B, Tadjkarimi S, Tornebrandt K, Yacoub MH (1990) 5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res 24:932–937
Connor HE, Feniuk W, Humphrey PPA (1989) 5-Hydroxytryptamine contracts human coronary arteries predominantly via 5-HT2 receptor activation. Eur J Pharmacol 161:91–94
Ellis AM, Coker SJ, Maxwell MP, Ford A, Hughes B (1988) Potential role of 5-HT1-like receptors in myocardial infarction and blood flow in a beagle dog model. Br J Pharmacol 95:493P
Frenken M, Kaumann AJ (1985) Ketanserin causes surmountable antagonism of 5-hydroxytryptamine-induced contractions in large coronary arteries of dog. Naunyn-Schmiedeberg's Arch Pharmacol 328:301–303
Hamblin MW, Metcalf MA (1991) Primary structure and functional characterisation of a human 5-HT1D-type serotonin receptor. Mol Pharmacol 40:143–148
Hartig PR, Branchek TA, Weinshank RL (1992) A subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci 13:152–159
Humphrey PPA, Feniuk W, Perren MJ, Connor HE, Oxford AW, Coates IH, Butina D (1988) GR 43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol 94:1123–1132
Kaumann AJ (1983) Yohimbine and rauwolscine inhibit 5-hydroxytryptamine-induced contraction of large coronary arteries of calf through blockade of 5-HT2 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 323:149–154
Kaumann AJ (1990) Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors. Naunyn-Schmiedeberg's Arch Pharmacol 342:619–622
Kaumann AJ, Brown AM (1990a) Allosteric modulation of arterial 5-HT2 receptors. In: Saxena PR, Wallis DI, Wouters W, Bevan P (eds) Cardiovascular pharmacology of 5-hydroxytryptamine. Prospective therapeutic applications. Kluwer, Dordrecht Boston London, pp 127–142
Kaumann AJ, Brown AM (1990b) Human coronary artery spasm induced by 5-hydroxytryptamine: role of receptor subtypes, plaque and stenosis. Naunyn-Schmiedeberg's Arch Pharmacol 341:R60
Kaumann AJ, Frenken M (1985) A paradox: the 5-HT2 receptor antagonist ketanserin restores the 5-HT-induced contraction depressed by methysergide in large coronary arteries of calf. Allosteric regulation of 5-HT2 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 328:295–300
Levy FO, Gudermann T, Perez-Reyes E, Birnbaumer M, Kaumann A, Birnbaumer L (1992) Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype. J Biol Chem 267:7553–7562
Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons M-J, Dumont JE, Vassart G (1989) Selective amplification and cloning of four members of the G protein-coupled receptor family. Science 244:569–572
Schoefter P, Hoyer D (1990) 5-Hydroxytryptamine (5-HT) induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther 252:387–395
Willet F, Curzen N, Adams J, Armitage M (1992) Coronary vasospasm induced by subcutaneous sumatriptan. Br Med J 304:1415
Zgombick JM, Weinshank RL, Macchi M, Schechter LE, Branchek TA, Hartig PR (1992) Expression and pharmacological characterisation of a canine 5-hydroxytryptamine1D receptor subtype. Mol Pharmacol 40:1036–1042
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Correspondence to A. J. Kaumann at the above address
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Parsons, A.A., Stutchbury, C., Raval, P. et al. Sumatriptan contracts large coronary arteries of beagle dogs through 5-HT1-like receptors. Naunyn-Schmiedeberg's Arch Pharmacol 346, 592–596 (1992). https://doi.org/10.1007/BF00169018
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DOI: https://doi.org/10.1007/BF00169018