Non-additivity of adrenaline and galanin effects on 86Rb 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 alpha 2-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 86Rb efflux was monitored in normal mouse islets perifused with a medium containing 15 mM glucose. At a maximally effective concentration of 10 microM, adrenaline partially repolarized the membrane, inhibited but did not abolish electrical activity, and caused a decrease in 86Rb efflux (due to a lesser activation of Ca(2+)- and voltage-activated K+ channels). In the presence of 10 microM adrenaline, galanin had no effect on membrane potential, electrical activity and 86Rb 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 86Rb efflux when added at a low concentration (15 microM) to a medium containing 10 microM adrenaline. At a high concentration (250 microM), diazoxide repolarized the membrane to the resting potential and markedly accelerated 86Rb efflux both in the presence and absence of adrenaline. The non-additivity of the effects of adrenaline and galanin suggests that alpha 2-adrenoceptors and galanin receptors share common targets in pancreatic B-cells.
Drews
G
G
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Detimary
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Henquin
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D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D019004:Galanin; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D012414:Rubidium Radioisotopes / Q000032:analysis*
D010455:Peptides; D012414:Rubidium Radioisotopes; D019004:Galanin; D005947:Glucose; D003981:Diazoxide; D004837:Epinephrine