Specificity of Serotonin Inhibition of Insulin Release from Golden Hamster Pancreas

Five-hydroxytryptamine (serotonin) inhibited basal and stimulated insulin release from pieces of golden hamster pancreas. Five-hydroxyindole acetic acid was a less potent inhibitor of insulin release than was serotonin, while 5- hydroxytryptophan and tryptamine had no effect on this process. In contrast, L-tryptophan potentiated high glucosemediated insulin release. Thus there was an absolute structural requirement for a hydroxyl group in the five position of the indole ring, and a relative requirement for an amine group in the alkyl chain for these indole compounds to be inhibitors of insulin release. In further studies, methysergide maleate, a specific serotonin inhibitor, blocked this action of serotonin. Methysergide maleate also stimulated glucose-mediated insulin release suggesting that endogenous serotonin may influence in vitro insulin secretion. Thus the inhibitory effect of serotonin on insulin secretion appears to be quite specific.