Structural Determinants of Indole Amine Action on in Vitro Insulin Release1

The structural specificity for inhibition of glucose stimulated insulin secretion by indole amines such as serotonin, was studied in an in vitro golden hamster pancreas system. Serotonin is the most potent inhibitor in this series, tryptamine is a weaker inhibitor of insulin release, while 5–methoxytryptamine, melatonin and 5–hydroxyindole acetic acid (S—HIAA) have no inhibitory activity. The inhibition of insulin secretion by serotonin is blocked by some (methysergide maleate) but not blocked by other (cinanserin) serotonin antagonists. It is concluded that in both the indole amine and catecholamine series there is a decrease in inhibitory potency with reduction of the number of hydroxyl groups on the aromatic ring; absence of the aliphatic amine group results in complete loss of inhibitory action.(Endocrinology91: 809, 1972)