Interference of carboxy-PTIO with nitric oxide- and peroxynitrite-mediated reactions.
Carboxy-PTIO reacts rapidly with NO to yield NO2 and has been used as a scavenger to test the importance of nitric oxide (NO) in various physiological conditions. This study investigated the effects of carboxy-PTIO on several NO- and peroxynitrite-mediated reactions. The scavenger potently inhibited NO-induced accumulation of cGMP in endothelial cells but potentiated the effect of the putative peroxynitrite donor SIN-1, Carboxy-PTIO completely inhibited peroxynitrite-induced formation of 3-nitrotyrosine from free tyrosine (EC50 = 36 +/- 5 microM) as well as nitration of bovine serum albumin. Peroxynitrite-mediated nitrosation of GSH was stimulated by the drug with an EC50 of 0.12 +/- 0.03 mM, whereas S-nitrosation induced by the NO donor DEA/NO (0.1 mM) was inhibited by the scavenger with an IC50 of 0.11 +/- 0.03 mM. Oxidation of NO with carboxy-PTIO resulted in formation of nitrite without concomitant production of nitrate. Our results demonstrate that the effects of carboxy-PTIO are diverse and question its claimed specificity as NO scavenger.
Pfeiffer
S
S
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Leopold
E
E
Hemmens
B
B
Schmidt
K
K
Werner
E R
ER
Mayer
B
B
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D001565:Benzoates; D016166:Free Radical Scavengers; D007093:Imidazoles; D009566:Nitrates; D009573:Nitrites; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; C039642:peroxynitric acid; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP