Effects of arginine analogues on nitric oxide synthase activity in the rat drain

As nitric oxide (NO) was synthesize by nitric oxide synthase (NOS) from L-arginine (Arg) which had guanidino group in its molecule, we examined the effect of 30 kinds of Arg analogues on NOS activity in the rat brain. None of compounds tested act as substrates of NOS. In the presence of equimolar Arg (100 mu M), N-G-methyl-L-arginine (MeArg) which was well known NOS inhibitor inhibit NOS activity to 37%. On the other hand, hirudonine, diamidinocystamine and guanethidine inhibited NOS activity to 64%, 67% and 74% respectively. Dimethylguanidine and N-aminobenzoylguanidine also showed weak inhibitory effect on NOS activity. Though almost of all NOS inhibitors reported previously were synthesized by substituting the guanidino nitrogen of Arg, guanidino nitrogens of hirudonine, diamidinocystamine and guanethidine were not substituted. They will be excellent drugs to investigate not only the chemical nature of NOS but also the physiologic function of NO in the brain.