Abstract
1. 5-Hydroxytryptamine (5-HT) relaxes rings of neonatal porcine isolated vena cava by both an endothelium-dependent and an endothelium-independent mechanism. The receptor mediating the latter response has been shown to be a 5-HT1-like receptor (positively coupled to adenylyl cyclase) located on the vascular smooth muscle. The features of the endothelium-dependent response to 5-HT in this preparation are now described. 2. In ring preparations contracted with the stable thromboxane-A2-mimetic, U-46619 (10 nM), and in the presence of the 5-HT2 receptor antagonist ketanserin (1 microM), low concentrations of 5-HT (1-100 nM) evoked an endothelium-dependent, rapid, 'spike-like' relaxation. Higher concentrations of 5-HT (0.1-10 microM) elicited a more sustained, but endothelium-independent relaxation. 3. Relaxation induced by low concentrations (1-100 nM) of 5-HT was abolished by endothelium removal, and was markedly (but not totally) inhibited by the guanylate cyclase inhibitor, methylene blue (10 microM) or by the inhibitor of endothelium-derived nitric oxide (NO) synthesis, L-NG-monomethylarginine (L-NMMA; 100-500 microM). 4. The endothelium-dependent response to 5-HT was mimicked by alpha-methyl-5-HT, 5-methoxytryptamine, tryptamine and 2-methyl-5-HT, but not by sumatriptan or 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT) at concentrations up to 10 microM. In contrast, relaxation evoked by 5-carboxamidotryptamine (5-CT) was endothelium-independent. 5. The endothelium-dependent relaxation induced by 5-HT or alpha-methyl-5-HT was antagonized by methysergide, methiothepin, cyproheptadine and metergoline, but not by ketanserin, spiperone, ondansetron, verapamil, cyanopindolol, mesulergine, ICS 205-930, or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Angus J. A., Cocks T. M. Endothelium-derived relaxing factor. Pharmacol Ther. 1989;41(1-2):303–352. doi: 10.1016/0163-7258(89)90112-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
- Leff P., Martin G. R., Morse J. M. Differential classification of vascular smooth muscle and endothelial cell 5-HT receptors by use of tryptamine analogues. Br J Pharmacol. 1987 Jun;91(2):321–331. doi: 10.1111/j.1476-5381.1987.tb10287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molderings G. J., Engel G., Roth E., Göthert M. Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery. Naunyn Schmiedebergs Arch Pharmacol. 1989 Sep;340(3):300–308. doi: 10.1007/BF00168514. [DOI] [PubMed] [Google Scholar]
- Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schoeffter P., Hoyer D. 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. 1990 Jan;252(1):387–395. [PubMed] [Google Scholar]
- Schoeffter P., Hoyer D. Is the sumatriptan (GR 43175)-induced endothelium-dependent relaxation of pig coronary arteries mediated by 5-HT1D receptors? Eur J Pharmacol. 1989 Jul 4;166(1):117–119. doi: 10.1016/0014-2999(89)90692-4. [DOI] [PubMed] [Google Scholar]
- Sumner M. J., Feniuk W., Humphrey P. P. Further characterization of the 5-HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava. Br J Pharmacol. 1989 May;97(1):292–300. doi: 10.1111/j.1476-5381.1989.tb11953.x. [DOI] [PMC free article] [PubMed] [Google Scholar]