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

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...

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Bibliographic Details
Published inArchives internationales de pharmacodynamie et de thérapie Vol. 329; no. 1; p. 121
Main Authors Briejer, M R, Akkermans, L M, Schuurkes, J A
Format Journal Article
LanguageEnglish
Published Belgium 01.01.1995
Subjects
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
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Summary: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.
ISSN:0003-9780