Potentiation of Insulin Secretion in Vitro by Serotonin Antagonists

Abstract

The present studies were designed to determine if endogenous pancreatic islet cell monoamines such as serotonin, dopamine and norepinephrine play a physiological role in controlling insulin secretion. With an in vitro rabbit pancreas system, the effects of both serotonin and catecholamine antagonists on basal and stimulated insulin release were studied. Methysergide maleate (Sansert) potentiated both glucose and tolbutamide-stimulated insulin secretion, but alone it had no effect on insulin release. Studies in which exogenous monoamines were added to the incubations demonstrated that methysergide, purported to be a specific serotonin antagonist, blocked inhibition of insulin secretion by dopamine, 1-norepinephrine, 1-epinephrine and 1-isoproterenol. Methysergide differed in action from the alpha adrenergic blocking drug, phenoxybenzamine, for although the latter was a more potent blocker of the inhibitory action of exogenous catecholamines on insulin secretion, it did not potentiate glucose-stimulated insulin secretion. Glucose-mediated insulin secretion was also potentiated by the serotonin antagonists, cinanserin and cyproheptadine. Exogenous serotonin (4 × 10-3 M) had only a weak action in inhibiting insulin secretion from rabbit pancreas. Methysergide (1 × 10-4 M) failed to block this inhibitory action. It is suggested that (1) serotonin antagonists are blocking the inhibitory action of an intracellular compartmentalized serotonin pool, (2) some other endogenous indoleamine is the inhibitory substance that is being blocked by the serotonin antagonists, or (3) the three serotonin antagonists are influencing glucose-mediated insulin release through some unknown mechanism that has nothing to do with serotonin.