Effect of aromatic nitroso-compounds on superoxide-generating activity in neutrophils.
Aromatic nitroso-compounds such as nitrosobenzene inhibited the respiratory burst of intact neutrophils induced by various stimulants, including phorbol 12-myristate 13-acetate and a chemotactic peptide. The compounds also inhibited NADPH-dependent oxygen consumption by cell-free preparations of neutrophils. This indicates that nitroso-compounds act directly on the NADPH-oxidase system. The inhibitory effects induced by several nitroso-compounds, 2-nitrosotoluene, nitrosobenzene, 4-nitrosophenol, and 1-nitrosopyrrolidine, were examined and their inhibition constants, the concentrations causing 50% reduction of oxygen consumption, were found to be 0.043, 0.173, 0.672, and 32.1 mM, respectively. These values correlated well with the hydrophobicity of the compounds: a more hydrophobic compound was a more potent inhibitor against NADPH oxidase, suggesting that the oxidase has a hydrophobic site(s) for interaction with the inhibitors.
Nakata
M
M
The Institute of Physical and Chemical Research (RIKEN), Saitama.
Nasuda-Kouyama
A
A
Isogai
Y
Y
Kanegasaki
S
S
Iizuka
T
T
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D002474:Cell-Free System; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009249:NADP / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology
D007093:Imidazoles; D009603:Nitroso Compounds; D011725:Pyridines; D013481:Superoxides; D014050:Toluene; D009249:NADP; C027669:4-nitrosotoluene; C029899:imidazole; C023666:pyridine; D013755:Tetradecanoylphorbol Acetate; C012456:nitrosobenzene