Nitric Oxide Signaling (NOS)

Nitric oxide synthase (NOS) inhibitors and related tools act on the enzymes that make nitric oxide from L-arginine. NOS was first isolated from rat brain in 1990 and shown to require calmodulin for its activity. Three isoforms exist, neuronal, endothelial and inducible NOS (iNOS), the last expressed mainly in activated immune cells. 1400W dihydrochloride, described in 1997 as a slow, tight-binding iNOS inhibitor, and GW274150 are used for isoform-selective studies. L-NIO dihydrochloride is an arginine analog that inhibits several isoforms. Asymmetric dimethylarginine is an endogenous NOS inhibitor that accumulates in chronic renal failure. 2,4-Diamino-6-hydroxypyrimidine blocks GTP cyclohydrolase I, which limits synthesis of the NOS cofactor tetrahydrobiopterin.