Nitrocatechols versus nitrocatecholamines as novel competitive inhibitors of neuronal nitric oxide synthase: lack of the aminoethyl side chain determines loss of tetrahydrobiopterin-antagonizing properties.
6-Nitrocatecholamines were recently described as novel neuronal nitric oxide synthase inhibitors competing with both L-arginine and tetrahydrobiopterin (BH(4)). We report now that simple nitrocatechols are also competitive inhibitors, lacking however BH(4)-antagonizing properties. It is argued that 6-nitrocatecholamines interact with the L-arginine- and BH(4)-binding sites through the nitrocatechol and aminoethyl moieties, respectively.
Palumbo
Anna
A
Laboratory of Biochemistry, Zoological Station "Anton Dohrn", Villa Comunale I-80121, Naples, Italy.
Napolitano
Alessandra
A
d'Ischia
Marco
M
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001665:Binding Sites; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry; D002395:Catecholamines / Q000737:chemistry* / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009574:Nitro Compounds / Q000737:chemistry* / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D000975:Antioxidants; D002395:Catecholamines; D002396:Catechols; D009574:Nitro Compounds; D020033:Protein Isoforms; D001708:Biopterins; D001120:Arginine; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C003402:sapropterin