Central antinociceptive effect of L-ornithine, a metabolite of L-arginine, in rats and mice.
L-Arginine produces central antinociception by acting as a precursor of kyotorphin (L-tyrosyl-L-arginine), a [Met5]enkephalin releaser. This study investigated the antinociceptive activity of L-ornithine, a metabolite of L-arginine. L-Ornithine given s.c. at 300-1000 mg/kg suppressed carrageenin-induced hyperalgesia in rats in a naloxone-reversible manner. L-Ornithine and L-arginine, when given i.c.v. at 10-100 mu g/mouse, elicited antinociception even in intact mice, the effects being abolished by naloxone or naltrindole, and potentiated by bestatin, an inhibitor of aminopeptidase and kyotorphinase. The antinociception induced by i.c.v. L-ornithine was also inhibited by i.c.v. L-leucyl-L-arginine, a kyotorphin receptor antagonist, but was resistant to intracisternal anti-kyotorphin serum. L-Tyrosyl-L-ornithine, a synthetic dipeptide, (1-10 mu g/mouse, i.c.v.), exerted kyotorphin-like antinociception in mice. These findings suggest that L-ornithine produces L-arginine-like antinociception via kyotorphin receptors. However, this effect does not appear to be mediated by kyotorphin itself, but most likely by L-tyrosyl-L-ornithine, a putative dipeptide.
Kawabata
A
A
Department of Pharmacology, Kinki University, Higashi-Osaka, Japan.
Iwatsubo
K
K
Takaya
S
S
Takagi
H
H
D000698:Analgesia; D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors; D002351:Carrageenan; D002956:Citrulline / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005079:Excipients; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007276:Injections, Intraventricular; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009952:Ornithine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats
D004151:Dipeptides; D005079:Excipients; D009292:Narcotic Antagonists; D011480:Protease Inhibitors; D002956:Citrulline; D009270:Naloxone; D009271:Naltrexone; D002351:Carrageenan; D001120:Arginine; D009952:Ornithine; C055382:naltrindole; D007930:Leucine; C012211:ubenimex