Propulsion in Guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors

J. G. Jin, A. E. Foxx-Orenstein, J. R. Grider

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Previous studies have shown that the intestinal peristaltic reflex initiated by mucosal stimulation is mediated by release of 5- hydroxytryptamine (HT) from enterochromaffin cells; 5-HT acts via 5-HT4 receptors in rat and human, and via both 5-HT4 and 5-HT3 receptors in guinea pig to activate intramural sensory neurons that release calcitonin gene-related peptide. In this study, selective agonists and antagonists were used to examine the involvement of 5-HT4 and 5-HT3 receptors in colonic propulsion. The velocity of propulsion was measured with artificial fecal pellets introduced into the orad end of an isolated guinea pig colonic segment. Control velocity ranged from 0.5 to 3.3 mm/s; mean ± S.E.M., 1.3 ± 0.1 mm/s. The 5-HT4 antagonist, GR 113808A, and the 5-HT3 antagonist, LY 278584, decreased the velocity of pellet propulsion in a concentration- dependent fashion (39 ± 2% and 47 ± 1% decrease at 10 μM, respectively). A combination of both antagonists (10 μM each) was additive, decreasing the velocity by 82 ± 3% to 84 ± 4%. The selective 5-HT4 agonists, HTF 919 and R093877, as well as 5-HT in the presence of the 5-HT(2a) antagonist, ketanserin, increased the velocity of propulsion in a concentration-dependent fashion with EC50s of 6.9 ± 0.1 nM, 37.4 ± 1.0 nM, and 3.9 ± 0.1 nM, respectively. Compared with HTF 919, R093877 was less potent and appeared to be a partial agonist. All three agonists were effective at submicromolar concentrations; at concentrations above 1 μM, there was no increase in the velocity of propulsion. We conclude that the presence of fecal pellets triggers the release of 5-HT, which acts via both 5-HT3 and 5-HT4 receptors to regulate propulsive activity in guinea pig colon.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number1
StatePublished - Jan 1999
Externally publishedYes

Fingerprint

Receptors, Serotonin, 5-HT3
prucalopride
Serotonin
Guinea Pigs
Colon
Receptors, Serotonin, 5-HT4
LY 278584
Serotonin 5-HT4 Receptor Antagonists
Serotonin 5-HT4 Receptor Agonists
Enterochromaffin Cells
Serotonin 5-HT3 Receptor Antagonists
Ketanserin
Serotonin Antagonists
Calcitonin Gene-Related Peptide
Sensory Receptor Cells
Reflex
tegaserod

ASJC Scopus subject areas

  • Pharmacology

Cite this

Propulsion in Guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors. / Jin, J. G.; Foxx-Orenstein, A. E.; Grider, J. R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 288, No. 1, 01.1999, p. 93-97.

Research output: Contribution to journalArticle

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