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 pr operties of N-G-amino-, N-G-methyl-, N-G-hydroxy-, N-G-ethyl-, N-G-all yl-, N-G,N-G-dimethyl-, N-G-methoxy-L-arginine, and several other L-ar ginine derivatives were compared in NOS purified from both macrophage and rat cerebellum, Also, these compounds were tested for their potent ial as alternate substrates by determining their ability to elicit NAD PH consumption by NOS. N-G-Methoxy-L-arginine appears to be an alterna te substrate for NOS, whereas most other L-arginine analogs, except fo r the biosynthetic intermediate N-G-hydroxy-L-arginine, do not elicit significant enzyme turnover. (C) 1994 Academic Press, Inc.