Characterization of the 5-hydroxytryptamine receptor type involved in inhibition of spontaneous activity of human isolated colonic circular muscle

Br J Pharmacol. 1994 Sep;113(1):143-50. doi: 10.1111/j.1476-5381.1994.tb16186.x.


1. Experiments were carried out to characterize pharmacologically the 5-hydroxytryptamine (5-HT) receptor types which mediate inhibition of spontaneous contractions of the intertaenial circular muscle in human isolated colon. 2. 5-HT caused a reproducible concentration-dependent inhibition of spontaneous contractions of the circular muscle of human colon in vitro with a mean EC50 value of 0.2 microM and 95% confidence limits of 0.1-0.5 microM. No evidence for a contractile action of 5-HT was found. Tetrodotoxin (TTX, 1.5 microM) caused a rightward shift of the concentration-response curve of 5-HT with a concentration-ratio of 2.9. 3. The inhibitory response to 5-HT was mimicked by several indoles with the rank order of potency 5-HT > 5-methoxytryptamine = alpha-methyl-5-HT > 5-carboxamidotryptamine >> 2-methyl-5-HT. 5-Hydroxyindalpine was inactive. 4. The substituted benzamides were agonists with the following rank order of potency, 5-HT > renzapride > zacopride > metoclopramide > cisapride. 5. The inhibitory responses to 5-HT were not inhibited by methysergide (10 microM) or methiothepin (1 microM), which are antagonists selective for 5-HT1-like and 5-HT2 receptors, nor by ondansetron (10 microM) which is an antagonist at 5-HT3 receptors. 6. The inhibitory responses induced by 5-HT and 5-methoxytryptamine were competitively antagonized by a weak 5-HT4 receptor antagonist, tropisetron, with pKB values of approximately 6. Tropisetron had no significant effect on the inhibitory response curve produced by isoprenaline (0.01-100 microM). 7. The pharmacological profile of the 5-HT-evoked relaxations of human colon circular muscle are consistent with activation of a 5-HT4-like receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cocaine / pharmacology
  • Colon / drug effects*
  • Humans
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Pargyline / pharmacology
  • Receptors, Serotonin / drug effects*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Tetrodotoxin / pharmacology


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Tetrodotoxin
  • Pargyline
  • Cocaine