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.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
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Kawabata
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Tanaka
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Muguruma
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Takagi
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000187:drug effects; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000187:drug effects; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; C025025:alpha-methylornithine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D009955:Ornithine Decarboxylase; D010453:Peptide Synthases; C052769:kyotorphin synthetase; D019331:NG-Nitroarginine Methyl Ester