PMID- 17988652
OWN - NLM
STAT- MEDLINE
DCOM- 20080407
LR  - 20131121
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 75
IP  - 3
DP  - 2008 Feb 1
TI  - (2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dimethoxybenzyl)butyrolactone 
      suppresses fMLP-induced superoxide production by inhibiting fMLP-receptor binding 
      in human neutrophils.
PG  - 688-97
AB  - This study investigated the mechanism underlying the inhibiting effect of 
      (2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dimethoxybenzyl) butyrolactone 
      (PP-6), a lignan from Piper philippinum, on superoxide anion production induced 
      by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) in human 
      neutrophils. Human neutrophils were stimulated with fMLP (1 microM), PMA (100 nM) 
      or leukotriene B(4) (LTB(4); 1 microM) and induced superoxide anion release. PP-6 
      specifically inhibited fMLP-induced superoxide anion production in a 
      concentration-dependent manner with an IC(50) value of 0.3+/-0.1 microM. 
      Intracellular signaling caused by fMLP, PMA or LTB(4) were evaluated. PP-6 
      specifically inhibited fMLP-induced intracellular calcium mobilization and ERK 
      (p42/p44), Akt and p38 phosphorylation. Moreover, PP-6 specifically inhibited 
      fMLP-induced Mac-1 expression without affecting this caused by LTB(4) or PMA. 
      PP-6 did not increase cAMP level in human neutrophils. PP-6 did not inhibit 
      superoxide anion production by NaF (20 mM), a direct activator of G-protein, the 
      target of the inhibitory action of PP-6 appears to be a component of the signal 
      transduction pathway upstream of G-protein. PP-6 inhibited FITC-fMLP binding to 
      neutrophils in a concentration-dependent manner with an IC(50) of 1.5+/-0.2 
      microM. PP-6 did not bring a parallel shift in the concentration response of 
      fMLP-induced superoxide anion. Additionally, the inhibiting effect of PP-6 on 
      fMLP-induced superoxide anion was reversed when PP-6 was washed out. These 
      experimental results suggest that PP-6 exerts non-competitive and reversible 
      antagonistic effect on fMLP receptor.
FAU - Huang, Yi-Jia
AU  - Huang YJ
AD  - Graduate Institute of Natural Products, College of Medicine, Chang Gung 
      University, Taiwan.
FAU - Chen, Ih-Sheng
AU  - Chen IS
FAU - Tseng, Ching-Ping
AU  - Tseng CP
FAU - Day, Yuan-Ji
AU  - Day YJ
FAU - Lin, Yin-Chou
AU  - Lin YC
FAU - Liao, Chang-Hui
AU  - Liao CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071006
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 ((2R,3R)-2-(3',4'-dihydroxybenzyl)-3-(3'',4''-dimethoxybenzyl)butyrolactone)
RN  - 0 (Lignans)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - OL659KIY4X (4-Butyrolactone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 4-Butyrolactone/*analogs & derivatives/pharmacology
MH  - Adult
MH  - Calcium/metabolism
MH  - Cyclic AMP/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Humans
MH  - Lignans/*pharmacology
MH  - Macrophage-1 Antigen/analysis
MH  - Male
MH  - N-Formylmethionine Leucyl-Phenylalanine/*antagonists & inhibitors
MH  - Neutrophils/drug effects/metabolism
MH  - Phosphorylation
MH  - Piper/*chemistry
MH  - Receptors, Formyl Peptide/*antagonists & inhibitors/metabolism
MH  - Superoxides/*metabolism
EDAT- 2007/11/09 09:00
MHDA- 2008/04/09 09:00
CRDT- 2007/11/09 09:00
PHST- 2007/08/11 00:00 [received]
PHST- 2007/09/20 00:00 [revised]
PHST- 2007/10/01 00:00 [accepted]
PHST- 2007/11/09 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2007/11/09 09:00 [entrez]
AID - S0006-2952(07)00673-9 [pii]
AID - 10.1016/j.bcp.2007.10.002 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2008 Feb 1;75(3):688-97. doi: 10.1016/j.bcp.2007.10.002. Epub 
      2007 Oct 6.