Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Mar;117(6):1325–1333. doi: 10.1111/j.1476-5381.1996.tb16732.x

Characterization of 5-hydroxytryptamine receptors mediating contractions in basilar arteries from stroke-prone spontaneously hypertensive rats.

Y Nishimura 1
PMCID: PMC1909781  PMID: 8882632

Abstract

1. The 5-hydroxytryptamine (5-HT) induced-contraction in ring preparations of basilar arteries from Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) was pharmacologically characterized in vitro. 2. Contractile responses to 5-HT (1 nM-100 nM) and their pD2 values in arteries from SHRSP at 6 months of age were significantly greater than those in age-matched WKY, although the maximum response did not differ between the two groups. 3. There were no significant differences in contractile responses to U-44619, endothelin-1, neuropeptide Y, and angiotensin II between WKY and SHRSP arteries. 4. Spiperone (1 nM-1 microM, a 5-HT2 receptor antagonist), produced biphasic displacement of the 5-HT curves in WKY and SHRSP arteries. The response to high concentrations of 5-HT was concentration-dependently antagonized by spiperone, while the response to low concentrations of 5-HT was resistant to blockade by spiperone, and the spiperone-resistant contractile responses induced by 5-HT were greater in SHRSP than in WKY. Ketanserin (1-100 nM, 5-HT2) also produced a biphasic shift of the 5-HT curves for both arteries. 5. Methiothepin (10 and 100 nM, 5-HT1 and 5-HT2) potently inhibited 5-HT-induced contractions in both groups. In addition, methiothepin (100 nM) produced a parallel shift to the right of the component of 5-HT-induced contractile responses that was resistant to blockade by spiperone in both groups. 6. The contractile effects of 5-HT in WKY and SHRSP arteries were not affected by MDL 72222 (1 microM, 5-HT3) and SDZ 205-557 (1 microM, 5-HT4). In addition, cocaine (10 microM), pargyline (50 microM), prazosin (10 microM), indomethacin (3 microM) and SQ 29,548 (1 microM) did not affect the contractile effects of 5-HT in either artery. 7. Contractile responses to 5-carboxamidotryptamine, CGS 12066B, pindolol and propranolol were greater in SHRSP arteries than in WKY arteries, whereas contractions in response to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), alpha-methyl-5-HT and 2-methyl-5-HT did not differ between the two groups. Cisapride failed to contract basilar arteries in both groups. Furthermore, a correlation analysis showed a highly significant correlation between the pD2 values of 5-HT agonists in WKY and SHRSP arteries and their published binding affinities at the 5-HT1B subtype. 8. These findings suggest that 5-HT elicits vasoconstriction in rat basilar arteries by stimulation of a mixed receptor population of 5-HT2 and 5-HT1-like receptors (similar to the 5-HT1B receptor subtype), and that the contraction mediated by 5-HT1-like receptors is enhanced in the basilar artery from SHRSP.

Full text

PDF
1325

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Adham N., Ellerbrock B., Hartig P., Weinshank R. L., Branchek T. Receptor reserve masks partial agonist activity of drugs in a cloned rat 5-hydroxytryptamine1B receptor expression system. Mol Pharmacol. 1993 Mar;43(3):427–433. [PubMed] [Google Scholar]
  3. Bockaert J., Fozard J. R., Dumuis A., Clarke D. E. The 5-HT4 receptor: a place in the sun. Trends Pharmacol Sci. 1992 Apr;13(4):141–145. doi: 10.1016/0165-6147(92)90051-7. [DOI] [PubMed] [Google Scholar]
  4. Bonvento G., MacKenzie E. T., Edvinsson L. Serotonergic innervation of the cerebral vasculature: relevance to migraine and ischaemia. Brain Res Brain Res Rev. 1991 Sep-Dec;16(3):257–263. doi: 10.1016/0165-0173(91)90009-w. [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. Buchheit K. H., Gamse R., Pfannkuche H. J. SDZ 205-557, a selective antagonist at 5-HT4 receptors in the isolated guinea pig ileum. Eur J Pharmacol. 1991 Aug 6;200(2-3):373–374. doi: 10.1016/0014-2999(91)90601-l. [DOI] [PubMed] [Google Scholar]
  7. Chang J. Y., Hardebo J. E., Owman C. Differential vasomotor action of noradrenaline, serotonin, and histamine in isolated basilar artery from rat and guinea-pig. Acta Physiol Scand. 1988 Jan;132(1):91–102. doi: 10.1111/j.1748-1716.1988.tb08302.x. [DOI] [PubMed] [Google Scholar]
  8. Chang J. Y., Owman C. Involvement of specific receptors and calcium mechanisms in serotonergic contractile response of isolated cerebral and peripheral arteries from rats. J Pharmacol Exp Ther. 1987 Aug;242(2):629–636. [PubMed] [Google Scholar]
  9. Connor H. E., Feniuk W., Humphrey P. P. Characterization of 5-HT receptors mediating contraction of canine and primate basilar artery by use of GR43175, a selective 5-HT1-like receptor agonist. Br J Pharmacol. 1989 Feb;96(2):379–387. doi: 10.1111/j.1476-5381.1989.tb11828.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Craig D. A., Martin G. R. 5-HT1B receptors mediate potent contractile responses to 5-HT in rat caudal artery. Br J Pharmacol. 1993 Jul;109(3):609–611. doi: 10.1111/j.1476-5381.1993.tb13615.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deckert V., Angus J. A. Evidence that 5-HT2 receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine. Eur J Pharmacol. 1992 Oct 6;221(1):17–25. doi: 10.1016/0014-2999(92)90767-x. [DOI] [PubMed] [Google Scholar]
  12. Deckert V., Pruneau D., Elghozi J. L. Mediation by 5-HT1D receptors of 5-hydroxytryptamine-induced contractions of rabbit middle and posterior cerebral arteries. Br J Pharmacol. 1994 Jul;112(3):939–945. doi: 10.1111/j.1476-5381.1994.tb13171.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Descombes J. J., Devys M., Laubie M., Verbeuren T. J. Endothelial thromboxane production plays a role in the contraction caused by 5-hydroxytryptamine in rat basilar arteries. Eur J Pharmacol. 1993 Oct 19;243(2):193–199. doi: 10.1016/0014-2999(93)90380-z. [DOI] [PubMed] [Google Scholar]
  14. Fozard J. R. MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1984 May;326(1):36–44. doi: 10.1007/BF00518776. [DOI] [PubMed] [Google Scholar]
  15. Frenken M. Evidence for two populations of 5-hydroxytryptamine receptors in dog basilar artery. J Pharmacol Exp Ther. 1989 Jul;250(1):379–387. [PubMed] [Google Scholar]
  16. Frenken M., Kaumann A. J. Ketanserin causes surmountable antagonism of 5-hydroxytryptamine-induced contractions of large coronary arteries of dog. Naunyn Schmiedebergs Arch Pharmacol. 1985 Jan;328(3):301–303. doi: 10.1007/BF00515557. [DOI] [PubMed] [Google Scholar]
  17. Gaw A. J., Wadsworth R. M., Humphrey P. P. Pharmacological characterisation of postjunctional 5-HT receptors in cerebral arteries from the sheep. Eur J Pharmacol. 1990 Apr 10;179(1-2):35–44. doi: 10.1016/0014-2999(90)90399-q. [DOI] [PubMed] [Google Scholar]
  18. Glusa E., Müller-Schweinitzer E. Heterogeneity of 5-HT receptor subtypes in isolated human femoral and saphenous veins. Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):133–136. doi: 10.1007/BF00169257. [DOI] [PubMed] [Google Scholar]
  19. Hamel E., Bouchard D. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites. Br J Pharmacol. 1991 Jan;102(1):227–233. doi: 10.1111/j.1476-5381.1991.tb12158.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hamel E., Fan E., Linville D., Ting V., Villemure J. G., Chia L. S. Expression of mRNA for the serotonin 5-hydroxytryptamine1D beta receptor subtype in human and bovine cerebral arteries. Mol Pharmacol. 1993 Aug;44(2):242–246. [PubMed] [Google Scholar]
  21. Hamel E., Grégoire L., Lau B. 5-HT1 receptors mediating contraction in bovine cerebral arteries: a model for human cerebrovascular '5-HT1D beta' receptors. Eur J Pharmacol. 1993 Sep 21;242(1):75–82. doi: 10.1016/0014-2999(93)90012-7. [DOI] [PubMed] [Google Scholar]
  22. Hamel E., Robert J. P., Young A. R., MacKenzie E. T. Pharmacological properties of the receptor(s) involved in the 5-hydroxytryptamine-induced contraction of the feline middle cerebral artery. J Pharmacol Exp Ther. 1989 Jun;249(3):879–889. [PubMed] [Google Scholar]
  23. Heistad D. D., Baumbach G. L. Cerebral vascular changes during chronic hypertension: good guys and bad guys. J Hypertens Suppl. 1992 Dec;10(7):S71–S75. [PubMed] [Google Scholar]
  24. Hoyer D., Clarke D. E., Fozard J. R., Hartig P. R., Martin G. R., Mylecharane E. J., Saxena P. R., Humphrey P. P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994 Jun;46(2):157–203. [PubMed] [Google Scholar]
  25. Hoyer D., Schoeffter P. 5-HT receptors: subtypes and second messengers. J Recept Res. 1991;11(1-4):197–214. doi: 10.3109/10799899109066399. [DOI] [PubMed] [Google Scholar]
  26. Jansen I., Olesen J., Edvinsson L. 5-Hydroxytryptamine receptor characterization of human cerebral, middle meningeal and temporal arteries: regional differences. Acta Physiol Scand. 1993 Feb;147(2):141–150. doi: 10.1111/j.1748-1716.1993.tb09483.x. [DOI] [PubMed] [Google Scholar]
  27. Miyamoto A., Sakota T., Nishio A. Characterization of 5-hydroxytryptamine receptors on the isolated pig basilar artery by functional and radioligand binding studies. Jpn J Pharmacol. 1994 Jul;65(3):265–273. doi: 10.1254/jjp.65.265. [DOI] [PubMed] [Google Scholar]
  28. Nakane T., Kawai K., Chiba S. Mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries. Jpn J Pharmacol. 1993 May;62(1):67–74. doi: 10.1254/jjp.62.67. [DOI] [PubMed] [Google Scholar]
  29. Neale R. F., Fallon S. L., Boyar W. C., Wasley J. W., Martin L. L., Stone G. A., Glaeser B. S., Sinton C. M., Williams M. Biochemical and pharmacological characterization of CGS 12066B, a selective serotonin-1B agonist. Eur J Pharmacol. 1987 Apr 7;136(1):1–9. doi: 10.1016/0014-2999(87)90772-2. [DOI] [PubMed] [Google Scholar]
  30. Nishimura Y., Usui H., Suzuki A., Kajimoto N., Yamanishi Y. Relaxant response of isolated basilar arteries to calcitonin gene-related peptide in stroke-prone spontaneously hypertensive rats. Jpn J Pharmacol. 1992 Jul;59(3):333–338. doi: 10.1254/jjp.59.333. [DOI] [PubMed] [Google Scholar]
  31. Ogletree M. L., Harris D. N., Greenberg R., Haslanger M. F., Nakane M. Pharmacological actions of SQ 29,548, a novel selective thromboxane antagonist. J Pharmacol Exp Ther. 1985 Aug;234(2):435–441. [PubMed] [Google Scholar]
  32. Parsons A. A., Whalley E. T. Evidence for the presence of 5-HT1-like receptors in rabbit isolated basilar arteries. Eur J Pharmacol. 1989 Dec 19;174(2-3):189–196. doi: 10.1016/0014-2999(89)90311-7. [DOI] [PubMed] [Google Scholar]
  33. Parsons A. A., Whalley E. T., Feniuk W., Connor H. E., Humphrey P. P. 5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of human isolated basilar artery. Br J Pharmacol. 1989 Feb;96(2):434–440. doi: 10.1111/j.1476-5381.1989.tb11835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Saxena P. R. Cardiovascular effects from stimulation of 5-hydroxytryptamine receptors. Fundam Clin Pharmacol. 1989;3(3):245–265. doi: 10.1111/j.1472-8206.1989.tb00455.x. [DOI] [PubMed] [Google Scholar]
  36. Schoeffter P., Hoyer D. 5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity. Pharmacological comparison with special reference to the effects of yohimbine, rauwolscine and some beta-adrenoceptor antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1989 Sep;340(3):285–292. doi: 10.1007/BF00168512. [DOI] [PubMed] [Google Scholar]
  37. Schoeffter P., Hoyer D. Interaction of arylpiperazines with 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors: do discriminatory 5-HT1B receptor ligands exist? Naunyn Schmiedebergs Arch Pharmacol. 1989 Jun;339(6):675–683. doi: 10.1007/BF00168661. [DOI] [PubMed] [Google Scholar]
  38. Soltis E. E., Bohr D. F. Cerebral vascular responsiveness in deoxycorticosterone acetate-salt hypertensive rats. Am J Physiol. 1987 Jan;252(1 Pt 2):H198–H203. doi: 10.1152/ajpheart.1987.252.1.H198. [DOI] [PubMed] [Google Scholar]
  39. Unsworth C. D., Molinoff P. B. Regulation of the 5-hydroxytryptamine1B receptor in opossum kidney cells after exposure to agonists. Mol Pharmacol. 1992 Sep;42(3):464–470. [PubMed] [Google Scholar]
  40. Winquist R. J., Bohr D. F. Structural and functional changes in cerebral arteries from spontaneously hypertensive rats. Hypertension. 1983 May-Jun;5(3):292–297. doi: 10.1161/01.hyp.5.3.292. [DOI] [PubMed] [Google Scholar]
  41. Yokota Y., Imaizumi Y., Asano M., Matsuda T., Watanabe M. Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats. Br J Pharmacol. 1994 Sep;113(1):324–330. doi: 10.1111/j.1476-5381.1994.tb16212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. van Zwieten P. A. Pathophysiological relevance of serotonin. J Cardiovasc Pharmacol. 1987;10 (Suppl 3):S19–S25. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES