PMID- 2169942
OWN - NLM
STAT- MEDLINE
DCOM- 19901119
LR  - 20190510
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 100
IP  - 4
DP  - 1990 Aug
TI  - The effect of putative protein kinase C inhibitors, K252a and staurosporine, on 
      the human neutrophil respiratory burst activated by both receptor stimulation and 
      post-receptor mechanisms.
PG  - 819-25
AB  - 1. Two compounds, reported to be potent inhibitors of protein kinase C (PKC), 
      K252a and staurosporine, have been examined in order to gain further information 
      as to the possible role played by PKC in the signal transduction sequence of the 
      neutrophil respiratory burst as determined by superoxide (O2-) production. 2. A 
      number of stimuli were used in the study, some acting at receptors i.e. 
      fMet-Leu-Phe (fMLP), opsonized zymosan and heat-aggregated IgG (HAGG), one acting 
      on a G-protein, fluoride, and two direct PKC activators, dioctanoylglycerol 
      (diC8) and phorbol myristate acetate (PMA). 3. K252a and staurosporine inhibited 
      the respiratory burst with all the stimuli but the order of agonist sensitivity 
      was very different with the two inhibitors. 4. For K252a-induced inhibition of 
      O2- release, the order of potency was fluoride greater than fMLP, HAGG greater 
      than opsonized zymosan greater than PMA, DiC8. For staurosporine-induced 
      inhibition of O2- release, the order of potency changed to fluoride greater than 
      DiC8, PMA greater than HAGG, fMLP greater than opsonized zymosan. The 
      significance of this unexpected difference in relative rank order of potency is 
      discussed with reference to the reported mechanism of action of the two 
      inhibitors and the events involved in the oxidative burst. 5. Staurosporine at 
      low concentrations increased the fMLP-stimulated O2- response by 100%, the 
      maximum effect occurring at 35 nM. 6. To the extent that the compounds used are 
      specific inhibitors of PKC, these findings support a role for the enzyme PKC in 
      stimulus-activation coupling in O2- generation with all the stimuli used in this 
      study.
FAU - Twomey, B
AU  - Twomey B
AD  - Department of Pharmacology, University College London.
FAU - Muid, R E
AU  - Muid RE
FAU - Dale, M M
AU  - Dale MM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Alkaloids)
RN  - 0 (Carbazoles)
RN  - 0 (Indole Alkaloids)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - H88EPA0A3N (Staurosporine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Carbazoles/*pharmacology
MH  - Dimethyl Sulfoxide/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Indole Alkaloids
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*metabolism
MH  - Oxygen Consumption/*drug effects
MH  - Protein Kinase C/*antagonists & inhibitors
MH  - Staurosporine
MH  - Superoxides/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
PMC - PMC1917611
EDAT- 1990/08/01 00:00
MHDA- 1990/08/01 00:01
PMCR- 1991/08/01
CRDT- 1990/08/01 00:00
PHST- 1990/08/01 00:00 [pubmed]
PHST- 1990/08/01 00:01 [medline]
PHST- 1990/08/01 00:00 [entrez]
PHST- 1991/08/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1990.tb14098.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1990 Aug;100(4):819-25. doi: 10.1111/j.1476-5381.1990.tb14098.x.