Does protein kinase C regulate receptor agonists-mediated elevation in the cytosolic Ca2+ in human neutrophils?
The feedback regulation of elevated cytosolic free Ca2+ concentrations ([Ca2+]i) by protein kinase C (PKC) in neutrophils was studied by two approaches. First, the PKC-activity was induced by phorbol 12-myristate 13-acetate (PMA) before the stimulation of Ca2+-signal with N-formyl-methionyl-leucyl-phenylalanine and serum-opsonized zymosan particles. Pretreatment of cells with PMA inhibited agonists-dependent Ca(2+)-transients. This inhibition was reversed by staurosporine. Second, the PKC-activity was induced simultaneously with the Ca(2+)-signal by the receptor agonists. In these conditions staurosporine had no effect on the Ca(2+)-response. In addition, the enhancement of PKC-activity, obtained by accumulating the endogenous PKC-activator diacylglycerol (DAG) with a DAG-kinase inhibitor, failed to change the agonists-stimulated elevations of [Ca2+]i. It is concluded that activation of PKC by PMA inhibits neutrophil Ca(2+)-responses, whereas receptor-mediated activation of PKC does not yield a negative feedback in elevated [Ca2+]i.
Tuominen
H
H
Department of Biochemistry and Pharmacy, Abo Academy University, Turku, Finland.
Leino
L
L
Akerman
K E
KE
D000470:Alkaloids / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000201:enzymology*; D009895:Opsonin Proteins; D011493:Protein Kinase C / Q000097:blood*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D000470:Alkaloids; D009895:Opsonin Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium