PMID- 11259567
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20191210
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 297
IP  - 1
DP  - 2001 Apr
TI  - Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced 
      superoxide production by inhibiting fMLP-receptor binding in human neutrophils.
PG  - 388-94
AB  - The purpose of the present work was to investigate the mechanism underlying the 
      inhibitory action of rebamipide on superoxide anion (O2) production induced by 
      the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) in human 
      neutrophils. Phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), a product of 
      phosphoinositide 3-OH-kinase (PI 3-kinase) accumulated in response to fMLP and 
      this accumulation was well correlated with O2 production in human neutrophils. 
      Rebamipide inhibited PIP(3) production in parallel with the inhibition of 
      fMLP-induced O2 production. PI 3-kinase activity in anti-PI 3-kinase p85 
      immunoprecipitates was not affected by the presence of rebamipide, therefore 
      rebamipide did not have a direct inhibitory action on PI 3-kinase activity. Since 
      rebamipide had no inhibitory effect on O2 production induced by NaF, a direct 
      activator of G protein, the target of the inhibitory action of rebamipide appears 
      to be a component of the signal transduction pathway upstream of G protein. 
      Scatchard analysis of [3H]fMLP binding to human neutrophil membrane revealed that 
      rebamipide increased the K(D) value of [3H]fMLP without altering the number of 
      [3H]fMLP binding sites, suggesting that rebamipide has a competitive antagonistic 
      action against the fMLP-receptor. The competitive antagonistic action was further 
      confirmed by the finding that rebamipide caused a parallel shift to the right in 
      the dose-response curve of O2 production induced by fMLP. These results provide 
      evidence that the competitive inhibitory action of rebamipide on the 
      fMLP-receptor plays a main role in its inhibitory action on fMLP-induced O2 
      production.
FAU - Nagano, C
AU  - Nagano C
AD  - Third Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., 463-10, 
      Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. c_nagano@research.otsuka.co.jp
FAU - Azuma, A
AU  - Azuma A
FAU - Ishiyama, H
AU  - Ishiyama H
FAU - Sekiguchi, K
AU  - Sekiguchi K
FAU - Imagawa, K
AU  - Imagawa K
FAU - Kikuchi, M
AU  - Kikuchi M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Quinolones)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Peptide)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - LR583V32ZR (rebamipide)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/*analogs & derivatives/*pharmacology
MH  - Anti-Ulcer Agents/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Helicobacter pylori/drug effects/physiology
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/*antagonists & inhibitors/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphatidylinositol Phosphates/biosynthesis
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Quinolones/*pharmacology
MH  - Receptors, Formyl Peptide
MH  - Receptors, Immunologic/*metabolism
MH  - Receptors, Peptide/*metabolism
MH  - Superoxides/*metabolism
EDAT- 2001/03/22 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/03/22 10:00
PHST- 2001/03/22 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/03/22 10:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2001 Apr;297(1):388-94.