Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jan;102(1):107–112. doi: 10.1111/j.1476-5381.1991.tb12140.x

Further characterization, by use of tryptamine and benzamide derivatives, of the putative 5-HT4 receptor mediating tachycardia in the pig.

C M Villalón 1, M O den Boer 1, J P Heiligers 1, P R Saxena 1
PMCID: PMC1917868  PMID: 2043916

Abstract

1. It has recently been shown that the tachycardic response to 5-hydroxytryptamine (5-HT) in the anaesthetized pig, being mimicked by 5-methoxytryptamine and renzapride and blocked by high doses of ICS 205-930, is mediated by the putative 5-HT4 receptor. In the present investigation we have further characterized this receptor. 2. Intravenous bolus injections of the tryptamine derivatives, 5-HT (3, 10 and 30 micrograms kg-1), 5-methoxytryptamine (3, 10 and 30 micrograms kg-1) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT; 3, 10, 30 and 100 micrograms kg-1), resulted in dose-dependent increases in heart rate of, respectively, 25 +/- 2, 48 +/- 3 and 68 +/- 3 beats min-1 (5-HT; n = 35); 15 +/- 1, 32 +/- 2 and 57 +/- 3 beats min-1 (5-methoxytryptamine; n = 30); 6 +/- 4, 18 +/- 6, 34 +/- 6 and 64 +/- 11 beats min-1 (alpha-methyl-5-HT; n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
111

Selected References

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

  1. Blandina P., Goldfarb J., Green J. P. Activation of a 5-HT3 receptor releases dopamine from rat striatal slice. Eur J Pharmacol. 1988 Oct 18;155(3):349–350. doi: 10.1016/0014-2999(88)90528-6. [DOI] [PubMed] [Google Scholar]
  2. Bom A. H., Duncker D. J., Saxena P. R., Verdouw P. D. 5-Hydroxytryptamine-induced tachycardia in the pig: possible involvement of a new type of 5-hydroxytryptamine receptor. Br J Pharmacol. 1988 Mar;93(3):663–671. doi: 10.1111/j.1476-5381.1988.tb10324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clarke D. E., Craig D. A., Fozard J. R. The 5-HT4 receptor: naughty, but nice. Trends Pharmacol Sci. 1989 Oct;10(10):385–386. doi: 10.1016/0165-6147(89)90177-6. [DOI] [PubMed] [Google Scholar]
  4. Connor H. E., Feniuk W., Humphrey P. P., Perren M. J. 5-Carboxamidotryptamine is a selective agonist at 5-hydroxytryptamine receptors mediating vasodilatation and tachycardia in anaesthetized cats. Br J Pharmacol. 1986 Feb;87(2):417–426. doi: 10.1111/j.1476-5381.1986.tb10832.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Craig D. A., Clarke D. E. Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor. J Pharmacol Exp Ther. 1990 Mar;252(3):1378–1386. [PubMed] [Google Scholar]
  6. Dumuis A., Bouhelal R., Sebben M., Bockaert J. A 5-HT receptor in the central nervous system, positively coupled with adenylate cyclase, is antagonized by ICS 205 930. Eur J Pharmacol. 1988 Jan 27;146(1):187–188. doi: 10.1016/0014-2999(88)90503-1. [DOI] [PubMed] [Google Scholar]
  7. Dumuis A., Sebben M., Bockaert J. The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):403–410. doi: 10.1007/BF00167041. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Hoyer D. Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res. 1988;8(1-4):59–81. doi: 10.3109/10799898809048978. [DOI] [PubMed] [Google Scholar]
  10. Kaumann A. J., Sanders L., Brown A. M., Murray K. J., Brown M. J. A 5-hydroxytryptamine receptor in human atrium. Br J Pharmacol. 1990 Aug;100(4):879–885. doi: 10.1111/j.1476-5381.1990.tb14108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kohli J. D., Glock D., Goldberg L. I. Selective DA2 versus DA1 antagonist activity of domperidone in the periphery. Eur J Pharmacol. 1983 Apr 22;89(1-2):137–141. doi: 10.1016/0014-2999(83)90618-0. [DOI] [PubMed] [Google Scholar]
  12. Martin G. R., Leff P., Cambridge D., Barrett V. J. Comparative analysis of two types of 5-hydroxytryptamine receptor mediating vasorelaxation: differential classification using tryptamines. Naunyn Schmiedebergs Arch Pharmacol. 1987 Oct;336(4):365–373. doi: 10.1007/BF00164867. [DOI] [PubMed] [Google Scholar]
  13. Richardson B. P., Engel G., Donatsch P., Stadler P. A. Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature. 1985 Jul 11;316(6024):126–131. doi: 10.1038/316126a0. [DOI] [PubMed] [Google Scholar]
  14. Sanger G. J. Increased gut cholinergic activity and antagonism of 5-hydroxytryptamine M-receptors by BRL 24924: potential clinical importance of BRL 24924. Br J Pharmacol. 1987 May;91(1):77–87. doi: 10.1111/j.1476-5381.1987.tb08985.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sanger G. J., Nelson D. R. Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron). Eur J Pharmacol. 1989 Jan 10;159(2):113–124. doi: 10.1016/0014-2999(89)90695-x. [DOI] [PubMed] [Google Scholar]
  16. Saxena P. R., Lawang A. A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors. Arch Int Pharmacodyn Ther. 1985 Oct;277(2):235–252. [PubMed] [Google Scholar]
  17. Saxena P. R., Mylecharane E. J., Heiligers J. Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; mediation of tachycardia by 5-HT1-like receptors. Naunyn Schmiedebergs Arch Pharmacol. 1985 Aug;330(2):121–129. doi: 10.1007/BF00499904. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Schuurkes J. A., Van Nueten J. M., Van Daele P. G., Reyntjens A. J., Janssen P. A. Motor-stimulating properties of cisapride on isolated gastrointestinal preparations of the guinea pig. J Pharmacol Exp Ther. 1985 Sep;234(3):775–783. [PubMed] [Google Scholar]
  20. Tricklebank M. D. Interactions between dopamine and 5-HT3 receptors suggest new treatments for psychosis and drug addiction. Trends Pharmacol Sci. 1989 Apr;10(4):127–129. doi: 10.1016/0165-6147(89)90157-0. [DOI] [PubMed] [Google Scholar]
  21. Van Nueten J. M., Janssen P. A., Van Beek J., Xhonneux R., Verbeuren T. J., Vanhoutte P. M. Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther. 1981 Jul;218(1):217–230. [PubMed] [Google Scholar]
  22. Villalón C. M., den Boer M. O., Heiligers J. P., Saxena P. R. Mediation of 5-hydroxytryptamine-induced tachycardia in the pig by the putative 5-HT4 receptor. Br J Pharmacol. 1990 Aug;100(4):665–667. doi: 10.1111/j.1476-5381.1990.tb14073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES