INTERFERENCE OF CARBOXY-PTIO WITH NITRIC OXIDE-MEDIATED 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 phy siological conditions. This study investigated the effects of carboxy- PTIO on several NO- and peroxynitrite-mediated reactions. The scavenge r potently inhibited NO-induced accumulation of cGMP in endothelial ce lls but potentiated the effect of the putative peroxynitrite donor SIN -1. Carboxy-PTIO completely inhibited peroxynitrite-induced formation of 3-nitrotyrosine from free tyrosine (EC(50) = 36 +/- 5 mu M) as well as nitration of bovine serum albumin. Peroxynitrite-mediated nitrosat ion of GSH was stimulated by the drug with an EC(50) 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 conc omitant production of nitrate. Our results demonstrate that the effect s of carboxy-PTIO are diverse and question its claimed specificity as NO scavenger. Copyright (C) 1997 by Elsevier Science Inc.