Correlation between plasma membrane potential and second messenger generation in the promyelocytic cell line HL-60.
The effects of plasma membrane depolarization on cytosolic free calcium ([Ca2+]i) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) generation were investigated in the human promyelocytic cell line HL-60 differentiated with either dimethyl sulfoxide or retinoic acid into neutrophil-like cells. Increases in [Ca2+]i and accumulation of Ins(1,4,5)P3 were triggered by two chemoattractants fMet-Leu-Phe and leukotriene B4. Plasma membrane potential was depolarized by isoosmotic substitution of NaCl with KCl, by the pore-forming ionophore gramicidin D, or by long term treatment with ouabain. Both Ca2+ mobilization from intracellular stores and Ca2+ influx across the plasma membrane were reduced by prior depolarization of plasma membrane potential regardless of the procedure employed to collapse it. Agonist-induced generation of Ins(1,4,5)P3 was also reduced in parallel in pre-depolarized HL-60 cells. The present findings provide further evidence suggesting that plasma membrane potential can be an important modulator of agonist-activated second messenger generation in myelocytic cells.
Infectious Diseases Division, University Hospital, Genève, Switzerland.
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Pittet
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Di Virgilio
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Pozzan
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Monod
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Lew
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008564:Membrane Potentials / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology*
D006096:Gramicidin; D004533:Egtazic Acid; D015759:Ionomycin; D014212:Tretinoin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010042:Ouabain; D011189:Potassium Chloride; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D004121:Dimethyl Sulfoxide