NG-nitro-L-arginine methyl ester and alpha-methyl-L-ornithine inhibit kyotorphin synthetase from rat brain.

Kyotorphin (KTP), an antinociceptive dipeptide (Tyr-Arg), is formed by KTP synthetase from L-Tyr and L-Arg in the brain. We examined the effects of various L-Arg analogues on immunoreactive KTP (iKTP) formation by KTP synthetase purified partially from rat brain. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), but not NG-nitro-L-arginine and N-iminoethyl-L-ornithine, suppressed iKTP formation by KTP synthetase from 1 mM of L-Arg and L-Tyr, the IC50 value being 2.33 mM. Similarly, alpha-methyl-L-ornithine (alpha-MO) inhibited KTP synthetase, the IC50 value being 2.51 mM. D-Arg at high concentrations also exhibited a weak inhibitory effect. Kinetic experiments indicated that the inhibition by L-NAME and alpha-MO of KTP synthetase is competitive. Thus, these L-Arg analogues appear to act as the competitive inhibitor of KTP synthetase.