Relationship of phosphatidylinositol bisphosphate hydrolysis to calcium mobilization and functional activation in fluoride-treated neutrophils.
Sodium fluoride (20 mM) effected rapid hydrolysis of phosphatidylinositol bisphosphate (PIP2) in human neutrophils. Intracellular free Ca2+ levels increased after PIP2 hydrolysis but before respiratory burst activation. Both the increase in intracellular free Ca2+ levels and the extent of functional activation were dependent on the availability of extracellular Ca2+. The rate of F(-)-stimulated PIP2 hydrolysis, however, was not affected when the rise in cytosolic Ca2+ was severely limited by depletion of extracellular Ca2+. Fluoride caused the specific hydrolysis of PIP2 in isolated neutrophil plasma membranes. This effect occurred in the presence of low levels of available Ca2+ and was accompanied by the release of inositol phosphates. We conclude that PIP2 hydrolysis is an early event in the response of neutrophils to F-. This response is not Ca2+-regulated but may lead to an influx of Ca2+ from the extracellular medium. Activation of a PIP2-specific phospholipase independent of a change in cytosolic free Ca2+ levels may be the initial event in the stimulus-response pathway triggered by fluoride.
D002118:Calcium / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D010743:Phospholipids / Q000097:blood; D012969:Sodium Fluoride / Q000494:pharmacology*
D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; C037178:phosphatidylinositol 4-phosphate; D012969:Sodium Fluoride; D002118:Calcium