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.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D004140:Dinitrophenols; D012701:Serotonin; D000968:Antimycin A; D005947:Glucose; D005033:Ethylmaleimide