The antinociceptive effects of endomorphin-1 and endomorphin-2 in diabetic mice.
The antinociceptive effects of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, were examined using the tail-flick test in non-diabetic and diabetic mice. Endomorphin-1, at doses of 1 to 10 microg, i.c.v., and endomorphin-2, at doses of 3 to 30 microg, i.c.v., each dose dependently inhibited the tail-flick response in both non-diabetic and diabetic mice. There was no significant difference between the antinociceptive effects of endomorphin-1 in non-diabetic mice and diabetic mice. The antinociceptive effect of endomorphin-2 was greater in non-diabetic mice than in diabetic mice. In non-diabetic mice, the antinociceptive effects of endomorphin-1 and endomorphin-2 were significantly reduced by beta-funaltrexamine, a mu-opioid receptor antagonist, and naloxonazine, a selective mu(1)-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist, or nor-binaltorphimine, a kappa-opioid receptor antagonist. In diabetic mice, the antinociceptive effect of endomorphin-2 was significantly reduced by beta-funaltrexamine and naloxonazine. However, these micro-opioid receptor antagonists had no significant effect on the antinociceptive effect of endomorphin-1 in diabetic mice. The antinociception induced by endomorphin-1 in diabetic mice was significantly reduced by naltrindole and 7-benzylidenenaltrexon, a selective delta(1)-opioid receptor antagonist, administered i.c.v. However, nor-binaltorphimine had no significant effect on the antinociceptive effects of endomorphin-1 and endomorphin-2 in diabetic mice. These results indicate that the antinociceptive effects of endomorphin-1 and endomorphin-2 in non-diabetic mice are mediated through the activation of mu(1)-opioid receptors, whereas in diabetic mice, endomorphin-1 and endomorphin-2 may produce antinociception through different actions at delta(1)- and mu(1)-opioid receptors, respectively.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, Japan. kamei@hoshi.ac.jp
Zushida
K
K
Ohsawa
M
M
Nagase
H
H
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine