guanosine-diphosphate and decamethrin

In mouse pancreatic beta-cells, extracellular ATP (0.1 mmol/l) effectively reduced glucose-induced insulin secretion. This inhibitory action resulted from a direct interference with the secretory machinery, and ATP suppressed depolarization-induced exocytosis by 60% as revealed by high-resolution capacitance measurements. Suppression of Ca2+-dependent exocytosis was mediated via binding to P2Y1 purinoceptors but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. Inhibition of exocytosis by ATP resulted from G-protein-dependent activation of the serine/threonine protein phosphatase calcineurin and was abolished by cyclosporin A and deltamethrin. In contrast to the direct inhibitory action on exocytosis, ATP reduced the whole-cell ATP-sensitive K+ (K(ATP)) current by 30% (via activation of cytosolic phospholipase A2), leading to membrane depolarization and stimulation of electrical activity. The stimulatory effect of ATP also involved mobilization of Ca2+ from thapsigargin-sensitive intracellular stores. We propose that the inhibitory action of ATP, by interacting with the secretory machinery at a level downstream to an elevation in [Ca2+]i, is important for autocrine regulation of insulin secretion in mouse beta-cells.

Topics: Adenosine Triphosphate; Adenylate Cyclase Toxin; Animals; Calcium; Cells, Cultured; Exocytosis; Female; Glucose; GTP-Binding Proteins; Guanosine Diphosphate; Insecticides; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Membrane Potentials; Mice; Mice, Inbred Strains; Nitriles; Permethrin; Phospholipases A; Phospholipases A2; Pyrethrins; Receptors, Purinergic P2; Receptors, Purinergic P2Y1; Thionucleotides; Tolbutamide; Uridine Triphosphate; Virulence Factors, Bordetella