PMID- 14667941
OWN - NLM
STAT- MEDLINE
DCOM- 20040129
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 67
IP  - 1
DP  - 2004 Jan 1
TI  - Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst 
      in human neutrophils by adrenaline: inhibition of Phospholipase A2 activity but 
      not p47phox phosphorylation and translocation.
PG  - 183-90
AB  - The polymorphonuclear neutrophil (PMN)-respiratory burst plays a key role in host 
      defense and inflammatory reactions. Modulation of this key neutrophil function by 
      endogenous agents and the mechanisms involved are poorly understood. This study 
      was designed to analyze the mechanisms involved in the effect of adrenaline on 
      neutrophil superoxide anions production. Using the superoxide dismutase 
      (SOD)-inhibitable cytochrome c reduction assay, we report here that the 
      beta-adrenergic agonist, adrenaline at physiologic concentrations (5-100 nM) 
      inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated but not 
      phorbol-myristate-acetate (PMA)-stimulated PMN superoxide anion production. The 
      inhibitory effect of adrenaline runs in parallel with an increase in 
      intracellular levels of cAMP which was reversed by the protein kinase A (PKA) 
      inhibitor H-89, suggesting a role for PKA in mediating the inhibitory effect of 
      adrenaline on fMLP-induced superoxide production. Adrenaline at physiological 
      concentrations did not inhibit the fMLP-stimulated membrane translocation of the 
      NADPH oxidase components p47phox and p67phox, nor the fMLP-stimulated 
      phosphorylation of p47phox. However, adrenaline strongly depressed the activity 
      of the cytosolic isoform of Phospholipase A(2) (cPLA(2)). We suggest that 
      adrenaline inhibits fMLP induced superoxide production upstream of the NADPH 
      oxidase via a mechanism involving PKA and cPLA(2).
FAU - O'Dowd, Yvonne M
AU  - O'Dowd YM
AD  - Department of Biochemistry, Conway Institute of Biomolecular and Biomedical 
      Research, University College Dublin, Belfield, 4, Dublin, Ireland.
FAU - El-Benna, Jamel
AU  - El-Benna J
FAU - Perianin, Axel
AU  - Perianin A
FAU - Newsholme, Philip
AU  - Newsholme P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Eicosanoic Acids)
RN  - 0 (Isoquinolines)
RN  - 0 (Phosphoproteins)
RN  - 0 (Sulfonamides)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
RN  - PQB8MJD4RB (arachidic acid)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Biological Transport
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - Eicosanoic Acids/pharmacology
MH  - Epinephrine/*pharmacology
MH  - Humans
MH  - Isoquinolines/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/*antagonists & inhibitors
MH  - NADPH Oxidases
MH  - Neutrophils/*drug effects/enzymology/metabolism
MH  - Phospholipases A/*metabolism
MH  - Phospholipases A2
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation/drug effects
MH  - Respiratory Burst/*drug effects/physiology
MH  - *Sulfonamides
EDAT- 2003/12/12 05:00
MHDA- 2004/01/30 05:00
CRDT- 2003/12/12 05:00
PHST- 2003/12/12 05:00 [pubmed]
PHST- 2004/01/30 05:00 [medline]
PHST- 2003/12/12 05:00 [entrez]
AID - S0006295203006701 [pii]
AID - 10.1016/j.bcp.2003.08.026 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2004 Jan 1;67(1):183-90. doi: 10.1016/j.bcp.2003.08.026.