Inhibition of arginase by NG-hydroxy-L-arginine in alveolar macrophages: implications for the utilization of L-arginine for nitric oxide synthesis.
The hypothesis was investigated that the nitric oxide (NO) synthase intermediate, NG-hydroxy-L-arginine (HOArg), is an arginase inhibitor in rabbit or rat alveolar macrophages. Exogenously applied HOArg strongly inhibited the arginase activity present in these cells (IC50 > or = 15 microM), and attenuated L-[3H]arginine transport (IC50 > or = 500 microM) in rabbit alveolar macrophages. Moreover, up to 37 microM HOArg were detected in the conditioned medium, but not in the lysate, of rat alveolar macrophages exposed to bacterial lipopolysaccharide for 18 h. HOArg may thus be a potent endogenous arginase inhibitor in these cells which increases the availability of L-arginine for NO biosynthesis.
Hecker
M
M
Center of Physiology, Johann Wolfgang Goethe University Clinic, Frankfurt am Main, Germany.
Nematollahi
H
H
Hey
C
C
Busse
R
R
Racké
K
K
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D009569:Nitric Oxide; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase