Inhibition by mepacrine and p-bromophenacylbromide of phosphoinositide hydrolysis,glucose oxidation,calcium uptake and insulin release in rat pancreatic islets

Mepacrine and p-bromophenacylbromide were both found to impair ³H-inositol phosphate production in response to both nutrient and hormone-neurotransmitter stimuli in islets prelabelled with ³H-inositol. Both drugs also inhibited net ⁴⁵Ca uptake in response to glucose or glibenclamide and considerably modified the patterns of ⁴⁵Ca and ⁸⁶Rb efflux from perifused islets under both basal and glucose-stimulated conditions. In addition, the oxidation of [U-¹⁴C] glucose in islets was impaired by either mepacrine or p-bromophenacylbromide. These inhibitory effects were found to be concentration-related for both mepacrine (0.01–1.0 mM) and p-bromophenacylbromide (0.03–0.3 mM) and were accompanied, in general, by a similar degree of inhibition of insulin secretion. These results suggest that both mepacrine and p-bromophenacylbromide can inhibit phospholipase C activity in intact islets, but also impair ⁴⁵Ca and ⁸⁶Rb fluxes and oxidation of nutrients. The diversity of these drugs' inhibitory actions makes them unsuitable tools for examining the role of specific cellular processes in the regulation of islet function.