PMID- 11992625
OWN - NLM
STAT- MEDLINE
DCOM- 20020517
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 63
IP  - 4
DP  - 2002 Feb 15
TI  - Inhibition of superoxide anion generation by YC-1 in rat neutrophils through 
      cyclic GMP-dependent and -independent mechanisms.
PG  - 577-85
AB  - 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a soluble guanylyl 
      cyclase (sGC) activator, inhibited formyl-methionyl-leucyl-phenylalanine 
      (fMLP)-induced superoxide anion (O(2)*(-)) generation and O(2) consumption in rat 
      neutrophils (IC(50) values of 12.7+/-3.1 and 17.7+/-6.9 microM, respectively). 
      Inhibition of O(2)*(-) generation by YC-1 was partially reversed by the cyclic 
      GMP-lowering agent 6-anilinoquinoline-5,8-quinone (LY83583) and by the Rp isomer 
      of 8-(4-chlorophenylthio)guanosine-3',5'-monophosphorothioate (Rp-8-pCPT-cGMPS), 
      a cyclic GMP-dependent protein kinase inhibitor. In cell-free systems, YC-1 
      failed to alter O(2)*(-) generation during dihydroxyfumaric acid autoxidation, 
      phorbol 12-myristate 13-acetate (PMA)-activated neutrophil particulate NADPH 
      oxidase preparation, and arachidonic acid-induced NADPH oxidase activation. YC-1 
      increased cellular cyclic GMP levels through the activation of sGC and the 
      inhibition of cyclic GMP-hydrolyzing phosphodiesterase activity. The plateau 
      phase, but not the initial spike, of fMLP-induced [Ca(2+)](i) changes was 
      inhibited by YC-1 (IC(50) about 15 microM). fMLP- but not PMA-induced 
      phospholipase D activation was inhibited by YC-1 (IC(50) about 28 microM). 
      Membrane-associated ADP-ribosylation factor and Rho A in cell activation was also 
      reduced by YC-1 at a similar concentration range. Neither cytosolic protein 
      kinase C (PKC) activity nor PKC membrane translocation was altered by YC-1. YC-1 
      did not affect either fMLP-induced phosphatidylinositol 3-kinase activation or 
      p38 mitogen-activated protein kinase phosphorylation, but slightly attenuated the 
      phosphorylation of extracellular signal-regulated kinase. Collectively, these 
      results indicate that the inhibition of the fMLP-induced respiratory burst by 
      YC-1 is mediated by cyclic GMP-dependent and -independent signaling mechanisms.
FAU - Wang, Jih Pyang
AU  - Wang JP
AD  - Department of Education and Research, Taichung Veterans General Hospital, 160 
      Chung Kang Road, Sec. 3, 407, ROC, Taichung, Taiwan. w1994@vghtc.gov.tw
FAU - Chang, Ling Chu
AU  - Chang LC
FAU - Raung, Shue Ling
AU  - Raung SL
FAU - Hsu, Mei Feng
AU  - Hsu MF
FAU - Huang, Li Jiau
AU  - Huang LJ
FAU - Kuo, Sheng Chu
AU  - Kuo SC
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 (Enzyme Activators)
RN  - 0 (Indazoles)
RN  - 11062-77-4 (Superoxides)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - H2D2X058MU (Cyclic GMP)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell-Free System/metabolism
MH  - Cyclic GMP/*metabolism
MH  - Enzyme Activators/pharmacology
MH  - In Vitro Techniques
MH  - Indazoles/*pharmacology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase D/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Respiratory Burst/drug effects
MH  - Superoxides/*metabolism
EDAT- 2002/05/07 10:00
MHDA- 2002/05/23 10:01
CRDT- 2002/05/07 10:00
PHST- 2002/05/07 10:00 [pubmed]
PHST- 2002/05/23 10:01 [medline]
PHST- 2002/05/07 10:00 [entrez]
AID - S0006295201008826 [pii]
AID - 10.1016/s0006-2952(01)00882-6 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2002 Feb 15;63(4):577-85. doi: 10.1016/s0006-2952(01)00882-6.