An enhancing effect of 5-hydroxytryptamine on electrically evoked atropine-resistant contraction of guinea-pig proximal colon

Br J Pharmacol. 1995 Jan;114(1):73-6. doi: 10.1111/j.1476-5381.1995.tb14907.x.


1. In the presence of atropine (0.2 microM) and indomethacin (2 microM), the effects of 5-hydroxytryptamine (5-HT) have been studied on electrically-evoked, neurogenic contractions of the guinea-pig proximal colon in vitro. 2. 5-HT, at higher concentrations than 1 nM, caused an increase in electrically (1 Hz, 0.3 ms, 160 mA)-evoked, atropine-resistant contractions in a concentration-dependent manner and at 30 nM produced a maximal effect (pEC50 value of 8.20 +/- 0.11, n = 6). The enhancing effects of 5-HT on the electrically evoked contractions were mimicked by alpha-methyl-5-HT (pEC50 value of 6.59 +/- 0.05, n = 6). 3. Both hexamethonium (100 microM) and spantide (10 microM), selective antagonists for nicotinic and tachykinin receptors respectively, significantly reduced the enhancement of the electrically evoked contractions by 5-HT (30 nM). 4. DAU 6285 (3 microM), a 5-HT4 receptor antagonist, abolished the enhancing action of 5-HT (30 nM), but metitepine (0.03 microM), a 5-HT1/5-HT2 receptor antagonist, ketanserin (0.01 microM), a 5-HT2 receptor antagonist, and ondansetron (1 microM), a 5-HT3 receptor antagonist, had no effect on the enhancement. The enhancing effects of alpha-methyl-5-HT (1 microM) were also abolished by DAU 6285 (3 microM). 5. Both 5-HT (30 nM) and alpha-methyl-5-HT (1 microM) had no effect on contractions to exogenous substance P (0.15-0.3 nM). 6. These results indicate that in the guinea-pig proximal colon, 5-HT produced an enhancement of atropine-resistant neurogenic contraction induced by electrical field stimulation through pre-junctional mechanisms and that the enhancement is mediated by the stimulation of 5-HT4 receptors located on intramural preganglionic cholinergic neurones and tachykininergic neurones.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Colon / physiology*
  • Electric Stimulation
  • Evoked Potentials / drug effects*
  • Guinea Pigs
  • Histamine / pharmacology
  • Male
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Tetrodotoxin / pharmacology


  • Serotonin Antagonists
  • Serotonin
  • Tetrodotoxin
  • Atropine
  • Histamine