L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia.
1. Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). 2. Subcutaneous administration of L-arginine (100-1,000 mg kg-1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin-induced hyperalgesia in a dose-dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective delta-opioid receptor antagonist (enkephalin antagonist), and D-arginine. 3. Intracerebroventricular administration of L-leucyl-L-arginine inhibited the antinociceptive effect of systemically administered L-arginine in hyperalgesic mice. 4. Intracerebroventricular administration of L-arginine (3 and 30 micrograms per mouse) and kyotorphin (300 ng-3 micrograms per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of L-arginine but not kyotorphin were blocked by intracerebroventricular administration of D-arginine. 5. These results suggest that L-arginine-induced antinociception is mediated by activation of 'kyotorphinergic' nerves followed by activation of the 'opioidergic' (possible 'enkephalinergic') nerves in the central nervous system.
Kawabata
A
A
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Nishimura
Y
Y
Takagi
H
H
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002351:Carrageenan; D004151:Dipeptides / Q000494:pharmacology; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D013237:Stereoisomerism
D000700:Analgesics; D004151:Dipeptides; D004723:Endorphins; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; C019448:kyotorphin; C078789:leucylarginine; D009271:Naltrexone; D002351:Carrageenan; D001120:Arginine; C055382:naltrindole