L-Tyrosine-induced antinociception in the mouse: involvement of central delta-opioid receptors and bulbo-spinal noradrenergic system.
L-Tyrosine methyl ester (L-Tyr-OMe) produces naloxone-reversible antinociception in mice. This effect was characterized in the present study. L-Tyr-OMe administered s.c. at doses of 100-400 mg/kg elicited dose-dependent antinociception, which was antagonized by s.c. and i.c.v. naloxone at 1 mg/kg and 10 ng/mouse, respectively, but not by i.t. injection at 10 ng/mouse. The antinociceptive effect of systemic L-Tyr-OMe was also inhibited by naltrindole (0.1 mg/kg s.c.), a selective delta-opioid receptor antagonist, but was resistant to L-leucyl-L-arginine (3 micrograms/mouse i.c.v.), a kyotorphin (L-tyrosyl-L-arginine) receptor antagonist. This effect was reduced by i.t., but not by i.c.v., phentolamine at 0.1-1 microgram/mouse, while methysergide (10 microgram/mouse i.t.) and p-chlorophenylalanine (500 mg/kg s.c.) did not have such an inhibitory effect. L-Tyr-OMe, given i.c.v. and i.t. at 0.1-10 microgram/mouse, also produced dose-dependent antinociception, the latter effect being naloxone-reversible but resistant to i.t. phentolamine. These results suggest that L-Tyr-OMe (s.c.)-induced antinociception is mediated by central delta-opioid receptors and by the bulbo-spinal noradrenergic system, but not by the central 'kyotorphinergic' system, and that L-Tyr-OMe, when given i.t., produces antinociception via spinal opioidergic, but not noradrenergic systems.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
A
A
Kawabata
K
K
Kasamatsu
H
H
Takagi
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C040444:tyrosine methyl ester; D014443:Tyrosine