Nonadditivity of Adrenaline and Galanin Effects On Rb-86 Efflux and Membrane-potential in Mouse B-cells Suggests Sharing of Common Targets

Adrenaline and galanin inhibit insulin release through strikingly similar mechanisms triggered by distinct receptors in pancreatic B cells. In this study we evaluated whether activation of alpha2-adrenoceptors and galanin receptors use a common or only a similar transduction pathway. The membrane potential of B-cells was measured with intracellular microelectrodes and Rb-86 efflux was monitored in normal mouse islets perifused with a medium containing 15 mM glucose. At a maximally effective concentration of 10 muM, adrenaline partially repolarized the membrane, inhibited but did not abolish electrical activity, and caused a decrease in Rb-86 efflux (due to a lesser activation of Ca2+- and voltage-activated K+ channels). In the presence of 10 muM adrenaline, galanin had no effect on membrane potential, electrical activity and Rb-86 efflux. Decreasing the concentration of glucose from 15 to 6 mM repolarized the B-cell membrane to the same extent as did adrenaline but did not prevent galanin from causing an additional hyperpolarization. In contrast to galanin, diazoxide, a selective opener of ATP-sensitive K+ channels still produced a small hyperpolarization and further decrease in Rb-86 efflux when added at a low concentration (15 muM) to a medium containing 10 muM adrenaline. At a high concentration (250 muM), diazoxide repolarized the membrane to the resting potential and markedly accelerated Rb-86 efflux both in the presence and absence of adrenaline. The non-additivity of the effects of adrenaline and galanin suggests that alpha2-adrenoceptors and galanin receptors share common targets in pancreatic B-cells