title: The dissociation of exocytosis and respiratory stimulation in leucocytes by ionophores.
abstract: By exploiting the unique characteristics of three ionophores, experimental conditions were found which permit the dissociation of respiratory stimulation from secretion in polymorphonuclear leucocytes. A marked stimulation of respiration was produced by ionophore X537A, which binds and transports both alkali-earth and alkali cations. The stimulatory activity of this ionophore was the same at either high or low Na+/K+ ratios in the medium and was virtually unaffected by extracellular Ca2+. A slight stimulation of oxygen consumption was also caused by the K+-selective ionophore valinomycin and by ionophore A23187, which complexes and transfers bivalent cations. Ionophore X537A and valinomycin were unable to stimulate selective release of granuleassociated beta-glucuronidase and gradually increased cell fragility, as monitored by increased leakage of lactate dehydrogenase. Ionophore A23187 slightly increased exocytosis of beta-glucuronidase. In a Mg2+-free medium, Ca2+, added simultaneously with ionophore A23187, greatly enhanced respiration and secretion of the granule enzyme. If Ca2+ was added a few minutes after the ionophore, exocytosis occurred, but no respiratory burst was observed. If the latter experiment was repeated in the presence of extracellular Mg2+, both secretion and respiration were stimulated. This effect was not produced by Mn2+ or Ba2+. It is proposed that Ca2+ is required for triggering selective secretion of granule enzymes from leucocytes is caused by an intracellular redistribution of cations, which may invovle Mg2+-dependent mechanisms.
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D005110:Extracellular Space; D005966:Glucuronidase / Q000032:analysis; D006168:Guinea Pigs; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007832:Lasalocid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D012156:Reticulocytes / Q000187:drug effects* / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D007476:Ionophores; D014634:Valinomycin; D000001:Calcimycin; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D008274:Magnesium; D002118:Calcium; D007832:Lasalocid