Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig small intestine

• Published in: Acta endocrinologica (Copenhagen) Vol. 124; no. 2; p. 203
• Main Authors: Racké, K, Schwörer, H, Agoston, D V, Kilbinger, H
• Format: Journal Article
• Language: English
• Published: Denmark 01-02-1991
• Subjects: Animals; Antibodies - pharmacology; Chromatography, High Pressure Liquid; Enterochromaffin Cells - drug effects; Enterochromaffin Cells - metabolism; Female; Guinea Pigs; Hydroxyindoleacetic Acid - metabolism; Intestine, Small - drug effects; Intestine, Small - metabolism; Kinetics; Male; Neurons - metabolism; Oxotremorine - pharmacology; Serotonin - metabolism; Tetrodotoxin - pharmacology; Vasoactive Intestinal Peptide - immunology; Vasoactive Intestinal Peptide - metabolism; Vasoactive Intestinal Peptide - pharmacology
• ISSN: 0001-5598
• DOI: 10.1530/acta.0.1240203

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.