Effects of metabolic inhibitors on the efflux of 5-hydroxytryptamine from pancreatic Beta-cells.

The influence of glucose and metabolic inhibitors on the efflux of tritiated 5-hydroxytryptamine (5-HT) was studied in perifused beta-cell-rich ob/ob mouse islets loaded with trace amounts of 3H-5-hydroxytryptophan. Glucose stimulated exocytotic release of 5-HT but the effect was rapidly inhibited by 2,4-dinitrophenol, antimycin A or N-ethylmalemide. This inhibition was followed by a marked stimulation of 5-HT efflux. The later phenomenon was reversible when 2,4-dinitrophenol was used by appeared irreversible with antimycin A or N-ethylmalemide. The results show that the maintenance of 5-HT within the beta-cell depends on energy. It is suggested that both inhibitory and stimulatory effects of 5-HT on insulin secretion depend on release of calcium from the secretory granules after short-circuiting a proton pump across the granule membrane.