Phorbol myristate acetate stimulates ATP-dependent calcium transport by the plasma membrane of neutrophils.
We studied the effect of phorbol myristate acetate (PMA) on the plasma membrane ATP-dependent calcium pump in neutrophils. Plasma membrane-enriched fractions ("podosomes") from PMA-stimulated guinea pig neutrophils exhibited a twofold stimulation of ATP-dependent calcium transport when compared with control podosomes. The stimulatory effect was rapid (beginning less than 2 min after exposure to PMA) and reached maximal values within 5 min. PMA increased the maximum velocity but not the affinity of the calcium pump for Ca++. Pump activation was not preceded by a rise in cytosolic free calcium concentration [Ca++]i, as assessed by the intracellularly trapped fluorescent calcium indicator Quin 2, but instead slightly lowered [Ca++]i and prevented the rise in [Ca++]i normally induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine. These results suggest that the calcium pump in the plasma membrane of neutrophils may be stimulated by calcium-independent pathways, and that this activation could be one of the earliest events mediating some of the effects of phorbol esters.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000634:Aminoquinolines; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D009504:Neutrophils / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D007473:Ion Channels; D010704:Phorbols; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; C035739:Quin2; D002118:Calcium