Abstract

1. Microfluorimetry techniques with fura-2 were used to characterize the effects of efaroxan (200 μM), phentolamine (200-500 μM) and idazoxan (200-500 μM) on the intracellular free Ca2+ concentration (Ca2+(i)) in mouse isolated islets of Langerhans. 2. The imidazoline receptor agonists efaroxan and phentolamine consistently elevated cytosolic Ca2+ by mechanisms that were dependent upon Ca2+ influx across the plasma membrane; there was no rise in Ca2+(i) when Ca2+ was removed from outside of the islets and diazoxide (100-250 μM) attenuated the responses. 3. Modulation of cytosolic Ca2+(i) by efaroxan and phentolamine was augmented by glucose (5-10 mM) which both potentiated the magnitude of the response and reduced the onset time of imidazoline-induced rises in Ca2+(i). 4. Efaroxan- and phentolamine-evoked increases in Ca2+(i) were unaffected by overnight pretreatment of islets with the imidazolines. Idazoxan failed to increase Ca2+(i) under any experimental condition tested. 5. The putative endogenous ligand of imidazoline receptors, agmatine (1 μM-1 mM), blocked K(ATP) channels in isolated patches of β-cell membrane, but effects upon Ca2+(i) could not be further investigated since agmatine disrupts fura-2 fluorescence. 6. In conclusion, the present study shows that imidazolines will evoke rises in Ca2+(i) in intact islets, and this provides an explanation to account for the previously described effects of imidazolines on K(ATP) channels, the cell membrane potential and insulin secretion in pancreatic β-cells.