Effects of metabolic inhibitors on the efflux of 5‐hydroxytryptamJne from pancreatic β‐cells

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Abstract
The influence of glucose and metabolic inhibitors on the efflux of tritiated 5‐hydroxytrypt‐amine (5‐HT) was studied in perifused β‐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 but appeared irreversible with antimycin A or N‐ethylmalemide. The results show that the maintenance of 5‐HT within the β‐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.