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. 1989 Feb;96(2):434–440. doi: 10.1111/j.1476-5381.1989.tb11835.x

5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of human isolated basilar artery.

A A Parsons 1, E T Whalley 1, W Feniuk 1, H E Connor 1, P P Humphrey 1
PMCID: PMC1854348  PMID: 2538194

Abstract

1. The 5-hydroxytryptamine (5-HT) receptor mediating contraction of endothelium denuded human basilar artery has been characterized in vitro. 2. 5-HT and a variety of 5-HT agonists contracted human isolated basilar artery with a rank order of agonist potency, 5-carboxamidotryptamine (5-CT) greater than 5-HT identical to methysergide greater than GR43175 much greater than 8-OHDPAT much greater than 2-methyl-5-HT. The maximum response produced by these agonists differed. 3. None of the agonists relaxed human basilar artery when tone was elevated with prostaglandin F2 alpha, indeed further contraction was seen. 4. The contractile responses of human basilar artery to 5-HT and the selective 5-HT1-like agonist GR43175 were highly reproducible whilst those to 5-CT were not. 5. The contractile response to both 5-HT and GR43175 was resistant to antagonism by ketanserin and GR38032, thus excluding activation of 5-HT2 and 5-HT3 receptors. The contractile action of 5-HT and GR43175 was also not antagonized by (+/-)-cyanopindolol, excluding the activation of receptors similar to 5-HT1A and 5-HT1B recognition sites identified in ligand binding studies. 6. In marked contrast, methiothepin was a potent antagonist of the contractile actions of both 5-HT and GR43175, with a pA2 value of 8.8 against both agonists. Methiothepin (100 nM) had no effect on the contractile response to the thromboxane A2-mimetic U46619. 7. We conclude that 5-HT and GR43175 contract the human isolated basilar artery by activating the same receptor type.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen G. S., Henderson L. M., Chou S. N., French L. A. Cerebral arterial spasm. 1. In vitro contractile activity of vasoactive agents on canine basilar and middle cerebral arteries. J Neurosurg. 1974 Apr;40(4):433–441. doi: 10.3171/jns.1974.40.4.0433. [DOI] [PubMed] [Google Scholar]
  3. Apperley E., Feniuk W., Humphrey P. P., Levy G. P. Evidence for two types of excitatory receptor for 5-hydroxytryptamine in dog isolated vasculature. Br J Pharmacol. 1980 Feb;68(2):215–224. doi: 10.1111/j.1476-5381.1980.tb10410.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Black J. W., Leff P. Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci. 1983 Dec 22;220(1219):141–162. doi: 10.1098/rspb.1983.0093. [DOI] [PubMed] [Google Scholar]
  5. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  6. Doenicke A., Brand J., Perrin V. L. Possible benefit of GR43175, a novel 5-HT1-like receptor agonist, for the acute treatment of severe migraine. Lancet. 1988 Jun 11;1(8598):1309–1311. doi: 10.1016/s0140-6736(88)92122-8. [DOI] [PubMed] [Google Scholar]
  7. Edvinsson L., Birath E., Uddman R., Lee T. J., Duverger D., MacKenzie E. T., Scatton B. Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine. Acta Physiol Scand. 1984 Jul;121(3):291–299. doi: 10.1111/j.1748-1716.1984.tb07459.x. [DOI] [PubMed] [Google Scholar]
  8. Edvinsson L., Hardebo J. E., Owman C. Pharmacological analysis of 5-hydroxytryptamine receptors in isolated intracranial and extracranial vessels of cat and man. Circ Res. 1978 Jan;42(1):143–151. doi: 10.1161/01.res.42.1.143. [DOI] [PubMed] [Google Scholar]
  9. Feniuk W. An analysis of 5-hydroxytryptamine receptors mediating contraction of isolated smooth muscle. Neuropharmacology. 1984 Dec;23(12B):1467–1472. doi: 10.1016/0028-3908(84)90090-x. [DOI] [PubMed] [Google Scholar]
  10. Feniuk W., Humphrey P. P., Perren M. J., Watts A. D. A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol. 1985 Nov;86(3):697–704. doi: 10.1111/j.1476-5381.1985.tb08948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feniuk W., Humphrey P. P., Watts A. D. 5-Hydroxytryptamine-induced relaxation of isolated mammalian smooth muscle. Eur J Pharmacol. 1983 Dec 9;96(1-2):71–78. doi: 10.1016/0014-2999(83)90530-7. [DOI] [PubMed] [Google Scholar]
  12. Forster C., Whalley E. T. Analysis of the 5-hydroxytryptamine induced contraction of the human basilar arterial strip compared with the rat aortic strip in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1982 Apr;319(1):12–17. doi: 10.1007/BF00491471. [DOI] [PubMed] [Google Scholar]
  13. Furchgott R. F., Cherry P. D., Zawadzki J. V., Jothianandan D. Endothelial cells as mediators of vasodilation of arteries. J Cardiovasc Pharmacol. 1984;6 (Suppl 2):S336–S343. doi: 10.1097/00005344-198406002-00008. [DOI] [PubMed] [Google Scholar]
  14. Heuring R. E., Peroutka S. J. Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci. 1987 Mar;7(3):894–903. doi: 10.1523/JNEUROSCI.07-03-00894.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hoyer D., Engel G., Kalkman H. O. Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol. 1985 Nov 26;118(1-2):13–23. doi: 10.1016/0014-2999(85)90658-2. [DOI] [PubMed] [Google Scholar]
  16. Humphrey P. P., Feniuk W., Perren M. J., Connor H. E., Oxford A. W., Coates L. H., Butina D. GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol. 1988 Aug;94(4):1123–1132. doi: 10.1111/j.1476-5381.1988.tb11630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Markowitz S., Saito K., Moskowitz M. A. Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache. Cephalalgia. 1988 Jun;8(2):83–91. doi: 10.1046/j.1468-2982.1988.0802083.x. [DOI] [PubMed] [Google Scholar]
  18. Middlemiss D. N., Fozard J. R. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151–153. doi: 10.1016/0014-2999(83)90230-3. [DOI] [PubMed] [Google Scholar]
  19. POOLE J. C., SANDERS A. G., FLOREY H. W. The regeneration of aortic endothelium. J Pathol Bacteriol. 1958 Jan;75(1):133–143. doi: 10.1002/path.1700750116. [DOI] [PubMed] [Google Scholar]
  20. Pazos A., Hoyer D., Palacios J. M. The binding of serotonergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol. 1984 Nov 27;106(3):539–546. doi: 10.1016/0014-2999(84)90057-8. [DOI] [PubMed] [Google Scholar]
  21. Peroutka S. J., Huang S., Allen G. S. Canine basilar artery contractions mediated by 5-hydroxytryptamine1A receptors. J Pharmacol Exp Ther. 1986 Jun;237(3):901–906. [PubMed] [Google Scholar]
  22. Taylor E. W., Duckles S. P., Nelson D. L. Dissociation constants of serotonin agonists in the canine basilar artery correlate to Ki values at the 5-HT1A binding site. J Pharmacol Exp Ther. 1986 Jan;236(1):118–125. [PubMed] [Google Scholar]
  23. Tranzer J. P., da Prada M., Pletscher A. Storage of 5-hydroxytryptamine in megakaryocytes. J Cell Biol. 1972 Jan;52(1):191–197. doi: 10.1083/jcb.52.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Trevethick M. A., Feniuk W., Humphrey P. P. 5-Carboxamidotryptamine: a potent agonist mediating relaxation and elevation of cyclic AMP in the isolated neonatal porcine vena cava. Life Sci. 1986 Apr 21;38(16):1521–1528. doi: 10.1016/0024-3205(86)90566-7. [DOI] [PubMed] [Google Scholar]

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