Effects of Serotonin, of its Biosynthetic Precursors and of the Anti-Serotonin Agent Metergoline on the Release of Glucagon and Insulin from Rat Pancreas

Abstract

We have evaluated the effect of serotonin (5-HT) and of its biosynthetic precursors 5-Hydroxytryptophan (5-HTP) and tryptophan (TRP) on the release of immunoreactive glucagon (IRG) and insulin (IRI) from isolated islets and pieces of pancreas of the rat. In isolated islets, 5-HT inhibited the IRI response to a high glucose concentration (3.0 mg/ml), without affecting the IRG response to either a low (0.5 mg/ ml) or a high glucose concentration; TRP stimulated the IRG and IRI response to the low glucose concentration, while 5-HTP was ineffective. When pieces of pancreas were used, 5-HT and 5-HTP inhibited IRG response to both glucose concentrations, while IRI release was inhibited only by 5-HT. The anti-5-HT agent metergoline enhanced the release of IRG and IRI by pieces of pancreas at both glucose concentrations. The results indicate that exogenous and endogenous 5-HT inhibit basal as well as glucose-mediated IRG and IRI release; that isolated islets are less sensitive than pieces of pancreas to the inhibitory effect of 5-HT and that TRP acts as an amino acid and not as a precursor of 5-HT. 1 Aided by Grant No. AM06034 from the National Institute of Arthritis, Metabolism and Digestive Diseases.