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 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.
Briejer
M R
MR
Department of Human and Animal Physiology, Wageningen Agricultural University, The Netherlands.
Akkermans
L M
LM
Schuurkes
J A
JA
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017829:Granisetron / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D001285:Atropine; D017829:Granisetron; D007211:Indoles; D007650:Ketanserin; D018377:Neurotransmitter Agents; D012701:Serotonin; D012702:Serotonin Antagonists; D000077526:Tropisetron