Desensitization by protein kinase C activation differentially uncouples formyl peptide receptors from effector enzymes in HL-60 granulocytes

Eleanor D. Lederer, Alfred A. Jacobs, Kenneth M. McLeish

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The hypothesis that protein kinase C (PKC) participates in agonist-mediated desensitization of formyl peptide receptors in HL-60 granulocytes was tested. fMet-Leu-Phe and leukotriene B4(LTB4) produced homologous desensitization of agonist-stimulated intracellular calcium transients. Pre-treatment with the PKC activator, phorbol myristate acetate (PMA; 10 nM), abolished both fMet-Leu-Phe and LTB4-stimulated calcium transients. Membranes prepared from control HL-60 granulocytes (NM) or cells treated with 10 nM PMA (PMA-M) demonstrated increased formyl peptide receptor and G protein density, as determined by radioligand binding and pertussis toxin- and cholera toxin-catalysed ADP ribosylation. fMet-Leu-Phe stimulation of guanosine 5′-[γ-thio]-triphosphate (GTPγS) binding and GTP hydrolysis and GDP inhibition of fMet-Leu-Phe binding were not different between NM and PMA-M. Pre-treatment with 10 nM PMA did not inhibit subsequent fMet-Leu-Phe-stimulated superoxide generation or phospholidase D activation. We conclude that PKC desensitizes fMet-Leu-Phe-stimulated phospholipase C, but not phospholipase D, responses and that PKC activation does not mediate agonist-induced desensitization of formyl peptide receptors.

Original languageEnglish (US)
Pages (from-to)735-745
Number of pages11
JournalCellular Signalling
Volume5
Issue number6
DOIs
StatePublished - Nov 1993
Externally publishedYes

Keywords

  • Desensitization
  • formyl peptides
  • G proteins
  • HL-60 granulocytes
  • intracellular calcium
  • phospholipase C
  • phospholipase D
  • protein kinase C

ASJC Scopus subject areas

  • Cell Biology

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