Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon

Arch Int Pharmacodyn Ther. 1995 Jan-Feb;329(1):121-33.


The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the guinea-pig isolated proximal colon were studied and analyzed. A classical organ bath setup was used to measure the longitudinal muscle responses isotonically. 5-Hydroxytryptamine induced concentration-dependent contractions which were preceded by relaxations at low concentrations. By means of the neurotoxin, tetrodotoxin, the muscarinic cholinoceptor antagonist, atropine, and selective 5-HT receptor antagonists, it was shown that the contractions to 5-HT are mediated by 5-HT2A receptors, localized on the smooth muscle, and by 5-HT3 and 5-HT4 receptors, localized on cholinergic nerves. The relaxation was abolished by tetrodotoxin and appeared to be mediated by two 5-HT receptor subtypes; the pharmacological profile of the high affinity 5-HT receptor resembled that of 5-HT2C receptors though it displayed also pronounced differences. Subsequently, it was shown that nitric oxide is the mediator released by lower concentrations of 5-HT, while, at higher concentrations, adenosine triphosphate could be involved as an end neurotransmitter as well. No evidence for a peptidergic neurotransmitter, such as vasoactive intestinal polypeptide, was obtained. Results with two 5-HT analogues confirmed the presence of a dual 5-HT receptor system (high and low affinity) regulating each the release of a different neurotransmitter (nitric oxide and adenosine triphosphate, respectively). The above described results stress the important role of 5-HT as a neurotransmitter involved in gastrointestinal motility.

Publication types

  • Review

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Colon / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Granisetron / pharmacology
  • Guinea Pigs
  • Indoles / pharmacology
  • Ketanserin / pharmacology
  • Neurotransmitter Agents / pharmacology*
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Tropisetron


  • Indoles
  • Neurotransmitter Agents
  • Serotonin Antagonists
  • Serotonin
  • Tropisetron
  • Atropine
  • Ketanserin
  • Granisetron