Relationship between efflux of ionic calcium and phosphorus during excitation of pancreatic islets with glucose.

Simultaneous rates of [32P]orthophosphate and 45Ca2+ efflux from prelabeled rat pancreatic islets have been evaluated to assess whether these ions move in concert throughout all phases of "stimulus-secretion coupling". Perifusion with stimulatory concentrations of glucose elicited immediate but transitory increases in 32P outflow accompanied by initial retardations and subsequent augmentations in net 45Ca2+ outflows. These monophasic 32P and biphasic 45Ca2+ responses to secretory stimulation were abolished completely by membrane stabilization with tetracaine. However, certain manipulations enabled individual components to be modified separately. During stimulation with glucose, inhibition of insulin release by Ni2+ abolished the late increases in 45Ca2+ outflow without affecting the initial retentions of 45Ca2+ or the increased releases of 32P. Under basal conditions, the ionophore A23187 "triggered" increased releases of 45Ca2+ and insulin without prior retentions of 45Ca2+ or enhancements of 32P efflux. Thus, the immediate retardations of 45Ca2+ outflow and heightened efflux of 32P may reflect early events in stimulus-secretion coupling which can be dissociated from the augmented release of 45Ca2+ accompanying activated emiocytosis.