title: Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig small intestine.
abstract: Isolated small intestinal segments of the guinea pig were arterially perfused and the release of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were intra-arterially applied. The muscarine receptor agonist oxotremorine (1 mumol/l) inhibited the release of 5-hydroxytryptamine by about 50%. In the presence of the neurotoxin tetrodotoxin, oxotremorine enhanced the release of 5-hydroxytryptamine by 145%, indicating that the inhibitory effect of oxotremorine was mediated by the release of a neurotransmitter. Exogenous vasoactive intestinal polypeptide (1-100 pmol/l) inhibited the release of 5-hydroxytryptamine by about 50%, an effect antagonized by a specific antibody to vasoactive intestinal polypeptide. This antibody to vasoactive intestinal polypeptide, on its own, had no effect on the release of 5-hydroxytryptamine. However, it prevented the inhibitory effect of oxotremorine. In the presence of the antibody to vasoactive intestinal polypeptide, unlike in the presence of tetrodotoxin, oxotremorine did not stimulate the release of 5-hydroxytryptamine. In conclusion, activation of neuronal muscarine receptors in the guinea pig small intestine enhances the release of several neurotransmitters which can inhibit the release of 5-hydroxytryptamine. The present experiments provide good evidence that vasoactive intestinal polypeptide is one of them.
authors.affiliation: Department of Pharmacology, University of Mainz, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Racké
authors.forename: H
authors.initials: H
authors.lastname: Schwörer
authors.forename: D V
authors.initials: DV
authors.lastname: Agoston
authors.forename: H
authors.initials: H
authors.lastname: Kilbinger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D010095:Oxotremorine