Oligopeptides as substrates and inhibitors for a new constitutive nitric oxide synthase from rat cerebellum.
A new constitutive nitric oxide synthase (NOS) that utilizes both L-arginine and bradykinin (BK) as substrates has been purified from rat cerebellum. This NOS is calmodulin-dependent with L-arginine, but calmodulin-independent with BK. Peptide products obtained using BK and a related nonapeptide as substrates were isolated and sequenced. Both N- and C-terminal arginines of BK are oxidized to citrullines by this enzyme. With BK as substrate NOS activity is competitively inhibited by NG-methyl-, NG-nitro-L-arginines, and a BK receptor antagonist. Our results suggest that oligopeptide-utilizing NOS may occur in other tissues, and show for the first time that oligopeptides can function as substrates or inhibitors of NOS.
Chen
Y
Y
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Rosazza
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019001:Nitric Oxide Synthase; D001920:Bradykinin