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. 1991 Dec;104(4):887–894. doi: 10.1111/j.1476-5381.1991.tb12522.x

Analysis of the 5-HT receptors mediating contractions in the rabbit isolated renal artery.

S Tadipatri 1, D van Heuven-Nolsen 1, W Feniuk 1, P R Saxena 1
PMCID: PMC1908853  PMID: 1667289

Abstract

1. Using a number of agonist and antagonist compounds, we have attempted to characterize the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT) in the rabbit isolated renal artery. 2. In vessel segments precontracted with the thromboxane-mimetic agent, U46619 (100 nM), neither 5-HT (10(-8) to 10(-4) M) nor 5-carboxamidotryptamine (5-CT; 10(-8) to 3 x 10(-4) M) caused relaxations like those observed with methacholine. Both 5-HT and 5-CT further increased the tone of the vessels, with pD2 values of 7.1 and 7.9, respectively. 3. In the absence of U46619, both 5-HT (10(-7) to 3 x 10(-3) M) and 5-CT (10(-7) to 10(-3) M) contracted the rabbit renal artery, but with reduced potencies. The contractions to 5-HT were reproducible and the rank order of potency (pD2) of the agonists was: alpha-methyl-5-HT (5.7), sumatriptan (5.3), 5-HT (5.1), 8-hydroxy-2(di-n-propylamino)tetralin (5.0), 5-CT (4.7) and 5-methoxytryptamine (4.3). 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane, flesinoxan and RU 24969 elicited either only small contractions or none at all. 4. The contractile effect of 5-HT was unaffected by MDL 72222 (10(-6) M) and metergoline (10(-8) and 10(-7) M), was weakly antagonized by ketanserin and phentolamine (pKB: 6.6 and 6.8, respectively), but was effectively antagonized by methiothepin (pKB: 8.6). Responses to 5-CT and sumatriptan were affected by ketanserin, phentolamine and methiothepin similarly to 5-HT-induced responses. 5. Ketanserin was ineffective against noradrenaline-induced contractions, which were antagonized by phentolamine with a pKB of 7.3.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Apperley E., Humphrey P. P., Levy G. P. Receptors for 5-hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta. Br J Pharmacol. 1976 Oct;58(2):211–221. doi: 10.1111/j.1476-5381.1976.tb10398.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aprigliano O., Hermsmeyer K. In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther. 1976 Sep;198(3):568–577. [PubMed] [Google Scholar]
  3. Black J. L., French R. J., Mylecharane E. J. Receptor mechanisms for 5-hydroxytryptamine in rabbit arteries. Br J Pharmacol. 1981 Nov;74(3):619–626. doi: 10.1111/j.1476-5381.1981.tb10472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blackshear J. L., Orlandi C., Hollenberg N. K. Serotonin and the renal blood supply: role of prostaglandins and the 5HT-2 receptor. Kidney Int. 1986 Sep;30(3):304–310. doi: 10.1038/ki.1986.185. [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. Caldicott W. J., Hollenberg N. K., Abrams H. L. Characteristics of response of renal vascular bed to contrast media. Evidence for vasoconstriction induced by renin-angiotensin system. Invest Radiol. 1970 Nov-Dec;5(6):539–547. doi: 10.1097/00004424-197011000-00021. [DOI] [PubMed] [Google Scholar]
  7. Charlton K. G., Bond R. A., Clarke D. E. An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Apparent distinction from the 5-HT1A, 5-HT1B and 5-HT1C subtypes. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jan;332(1):8–15. doi: 10.1007/BF00633190. [DOI] [PubMed] [Google Scholar]
  8. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [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. 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]
  12. 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]
  13. 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]
  14. Ismaiel A. M., Titeler M., Miller K. J., Smith T. S., Glennon R. A. 5-HT1 and 5-HT2 binding profiles of the serotonergic agents alpha-methylserotonin and 2-methylserotonin. J Med Chem. 1990 Feb;33(2):755–758. doi: 10.1021/jm00164a046. [DOI] [PubMed] [Google Scholar]
  15. Martin G. R., MacLennan S. J. Analysis of the 5-HT receptor in rabbit saphenous vein exemplifies the problems of using exclusion criteria for receptor classification. Naunyn Schmiedebergs Arch Pharmacol. 1990 Aug;342(2):111–119. doi: 10.1007/BF00166952. [DOI] [PubMed] [Google Scholar]
  16. McGrath M. A. 5-hydroxytryptamine and neurotransmitter release in canine blood vessels. Inhibition by low and augmentation by high concentrations. Circ Res. 1977 Oct;41(4):428–435. doi: 10.1161/01.res.41.4.428. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Peroutka S. J., McCarthy B. G. Sumatriptan (GR 43175) interacts selectively with 5-HT1B and 5-HT1D binding sites. Eur J Pharmacol. 1989 Apr 12;163(1):133–136. doi: 10.1016/0014-2999(89)90406-8. [DOI] [PubMed] [Google Scholar]
  20. Sahin-Erdemli I., Hoyer D., Stoll A., Seiler M. P., Schoeffter P. 5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of guinea-pig isolated iliac artery. Br J Pharmacol. 1991 Feb;102(2):386–390. doi: 10.1111/j.1476-5381.1991.tb12183.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Saxena P. R., Bom A. H., Verdouw P. D. Characterization of 5-hydroxytryptamine receptors in the cranial vasculature. Cephalalgia. 1989;9 (Suppl 9):15–22. doi: 10.1111/J.1468-2982.1989.TB00068.X. [DOI] [PubMed] [Google Scholar]
  22. Saxena P. R., Forsyth R. P., Johnston B. M., De Werk A. Regional and systemic haemodynamic changes evoked by 5-hydroxytryptamine in awake and anaesthetized rabbits. Eur J Pharmacol. 1978 Jul 1;50(1):61–68. doi: 10.1016/0014-2999(78)90253-4. [DOI] [PubMed] [Google Scholar]
  23. Saxena P. R., Villalón C. M. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol. 1990;15 (Suppl 7):S17–S34. [PubMed] [Google Scholar]
  24. Schoeffter P., Hoyer D. How selective is GR 43175? Interactions with functional 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):135–138. doi: 10.1007/BF00169219. [DOI] [PubMed] [Google Scholar]
  25. Shoji T., Tamaki T., Fukui K., Iwao H., Abe Y. Renal hemodynamic responses to 5-hydroxytryptamine (5-HT): involvement of the 5-HT receptor subtypes in the canine kidney. Eur J Pharmacol. 1989 Nov 21;171(2-3):219–228. doi: 10.1016/0014-2999(89)90110-6. [DOI] [PubMed] [Google Scholar]
  26. Sumner M. J., Humphrey P. P. 5-HT1D binding sites in porcine brain can be sub-divided by GR43175. Br J Pharmacol. 1989 Sep;98(1):29–31. doi: 10.1111/j.1476-5381.1989.tb16856.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vyden J. K., Lent D., Nagasawa K., Carvalho M., Serruya A., Corday E. The effect of serotonin on regional hemodynamics in the vascular system. J Clin Pharmacol. 1974 Aug-Sep;14(8):434–441. doi: 10.1002/j.1552-4604.1974.tb02325.x. [DOI] [PubMed] [Google Scholar]
  28. Wright C. E., Angus J. A. 5-carboxamidotryptamine elicits 5-HT2 and 5-HT3 receptor-mediated cardiovascular responses in the conscious rabbit: evidence for 5-HT release from platelets. J Cardiovasc Pharmacol. 1989 Apr;13(4):557–564. [PubMed] [Google Scholar]
  29. Wright C. E., Angus J. A. Diverse vascular responses to serotonin in the conscious rabbit: effects of serotonin antagonists on renal artery spasm. J Cardiovasc Pharmacol. 1987 Oct;10(4):415–423. doi: 10.1097/00005344-198710000-00006. [DOI] [PubMed] [Google Scholar]
  30. den Boer M. O., Villalón C. M., Heiligers J. P., Humphrey P. P., Saxena P. R. Role of 5-HT1-like receptors in the reduction of porcine cranial arteriovenous anastomotic shunting by sumatriptan. Br J Pharmacol. 1991 Feb;102(2):323–330. doi: 10.1111/j.1476-5381.1991.tb12173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van Heuven-Nolsen D., Tysse Klasen T. H., Luo Q. F., Saxena P. R. 5-HT1-like receptors mediate contractions of the rabbit saphenous vein. Eur J Pharmacol. 1990 Dec 4;191(3):375–382. doi: 10.1016/0014-2999(90)94171-s. [DOI] [PubMed] [Google Scholar]

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