Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine.
The effects of agonists and antagonists of 5-hydroxytryptamine (5-HT) receptors on the release of endogenous 5-HT from enterochromaffin cells were studied in the vascularly perfused isolated guinea-pig small intestine. The experiments were done in the presence of tetrodotoxin in order to exclude a neuronally mediated influence on 5-HT release. The 5-HT3 receptor agonist 2-methyl-5-HT increased 5-HT release, and this effect was antagonized by 1 nmol/l tropisetron. Nanomolar concentrations of tropisetron, MDL 72,222 and granisetron decreased 5-HT release. Ondansetron (0.1 and 1 mumol/l) did not modify 5-HT release. 5-Methoxytryptamine, BIMU8 and cisapride concentration-dependently inhibited 5-HT release. BIMU8 was more potent than 5-methoxytryptamine. Micromolar concentrations of tropisetron (1 and 10 mumol/l) enhanced the release, whilst methiothepine (0.1 mumol/l) did not affect the release of 5-HT. The results suggest that enterochromaffin cells of the guinea-pig ileum do not contain 5-HT1 and 5-HT2 receptors, but are endowed with 5-HT3 and 5-HT4 autoreceptors. Activation of the 5-HT3 receptors triggers a positive feedback mechanism leading to an increase of 5-HT release. The 5-HT3 receptors on the enterochromaffin cell differ from neuronal 5-HT3 receptors on guinea-pig myenteric plexus by their high affinity for tropisetron and MDL 72,222, and their very low affinity for ondansetron. Stimulation of 5-HT4 receptors causes inhibition of release; the inhibitory 5-HT4 receptor mechanism appears to predominate.
Gebauer
A
A
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany.
Merger
M
M
Kilbinger
H
H
D000818:Animals; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013779:Tetrodotoxin