Store-operated Ca Influx and Stimulation of Exocytosis in HL-60 Granulocytes*
نویسندگان
چکیده
This study addresses the role of store-operated Ca influx in the regulation of exocytosis in inflammatory cells. In HL-60 granulocytes, which do not possess voltage-operated Ca channels, the chemotactic peptide fMet-Leu-Phe (fMLP) was able to stimulate store-operated Ca influx and to trigger exocytosis of primary granules. An efficient triggering of exocytosis by fMLP required the presence of extracellular Ca and was inhibited by blockers of store-operated Ca influx. However, receptor-independent activation of store-operated Ca influx through thapsigargin did not trigger exocytosis. fMLP was unable to stimulate exocytosis in the absence of cytosolic free Ca concentration [Ca]c elevations. However, a second signal generated by fMLP synergized with store-operated Ca influx to trigger exocytosis and led to a left shift of the exocytosis/[Ca]c relationship in ionomycin-stimulated cells. The synergistic fMLP-generated signaling cascade was long-lasting, involved a pertussis toxin-sensitive G protein and a phosphatidylinositol 3-kinase. In summary, store-operated Ca influx is crucial for the efficient triggering of exocytosis in HL-60 granulocytes, but, as opposed to Ca influx through voltage-operated Ca channels in neurons, it is not a sufficient stimulus by itself and requires synergistic receptor-generated signals.
منابع مشابه
Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes.
This study addresses the role of store-operated Ca2+ influx in the regulation of exocytosis in inflammatory cells. In HL-60 granulocytes, which do not possess voltage-operated Ca2+ channels, the chemotactic peptide fMet-Leu-Phe (fMLP) was able to stimulate store-operated Ca2+ influx and to trigger exocytosis of primary granules. An efficient triggering of exocytosis by fMLP required the presenc...
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