Racke_1991_Acta.Endocrinol.(Copenh)_124_203

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.