H. Tuominen et al., DOES PROTEIN-KINASE-C REGULATE RECEPTOR AGONISTS-MEDIATED ELEVATION IN THE CYTOSOLIC CA2+ IN HUMAN NEUTROPHILS, Biochemical and biophysical research communications, 203(2), 1994, pp. 998-1004
The feedback regulation of elevated cytosolic free Ca2+ concentrations
([Ca2+](i)) by protein kinase C (PKC) in neutrophils was studied by t
wo approaches. First, the PKC-activity was induced by phorbol 12-myris
tate 13-acetate (PMA) before the stimulation of Ca2+-signal with N-for
myl-methionyl- leucyl-phenylalanine and serum-opsonized zymosan partic
les. Pretreatment of cells with PMA inhibited agonists-dependent Ca2+-
transients. This inhibition was reversed by staurosporine. Second, the
PKC-activity was induced simultaneously with the Ca2+-signal by the r
eceptor agonists. In these conditions staurosporine had no effect on t
he Ca2+-response. In addition, the enhancement of PKC-activity, obtain
ed by accumulating the endogenous PKC-activator diacylglycerol (DAG) w
ith a DAG-kinase inhibitor, failed to change the agonists-stimulated e
levations of [Ca2+](i). It is concluded that activation of PKC by PMA
inhibits neutrophil Ca2+-responses, whereas receptor-mediated activati
on of PKC does not yield a negative feedback in elevated[Ca2+](i). (C)
1994 Academic Press, Inc.