INHIBITION OF PURIFIED NITRIC-OXIDE SYNTHASE FROM RAT CEREBELLUM AND MACROPHAGE BY L-ARGININE ANALOGS

The inhibition of nitric oxide synthase (NOS) activity by a variety of L-arginine-related compounds has been investigated. The inhibitory properties of N-G-amino-, N-G-methyl-, N-G-hydroxy-, N-G-ethyl-, N-G-allyl-, N-G,N-G-dimethyl-, N-G-methoxy-L-arginine, and several other L-arginine derivatives were compared in NOS purified from both macrophage and rat cerebellum, Also, these compounds were tested for their potential as alternate substrates by determining their ability to elicit NADPH consumption by NOS. N-G-Methoxy-L-arginine appears to be an alternate substrate for NOS, whereas most other L-arginine analogs, except for the biosynthetic intermediate N-G-hydroxy-L-arginine, do not elicit significant enzyme turnover. (C) 1994 Academic Press, Inc.