The mixed antinociceptive agonist-antagonist activity of beta-endorphin(1-27) in mice.
beta-Endorphin(1-27) (i.c.v.) has been reported to inhibit the antinociceptive activity of i.c.v. administered beta-endorphin in mice. In this study the antagonist activity of beta-endorphin(1-27) has been confirmed and the antagonism appears to be mediated at delta 1 opioid receptors. At higher doses than that used for antagonism, i.c.v. administered beta-endorphin(1-27) was a full antinociceptive agonist. The antinociceptive activity of beta-endorphin is attributed to the release of met-enkephalin in the spinal cord and is antagonized by the selective delta 2 opioid receptor antagonist, naltriben (NTB) but not by the selective delta 1 opioid receptor antagonist, 7-benzylidenenaltrexone (BNTX). In contrast, the antinociceptive activity of i.c.v. administered beta-endorphin(1-27) was not affected by either NTB or BNTX administered i.c.v. or i.t. Also, the antinociceptive activity of beta-endorphin(1-27) was unaffected by the selective mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA) or the selective kappa opioid receptor antagonist, norbinaltorphimine (norBNI). Thus, beta-endorphin(1-27) appears to mediate antinociception supraspinally through the interaction of a unique receptor, i.e. a receptor that is different from mu, kappa, delta 1 or delta 2 opioid receptors. Alternatively, a non-opioid mechanism may be considered.
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
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AE
Takemori
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PS
Portoghese
D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D001615:beta-Endorphin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011957:Receptors, Opioid; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; C051844:norbinaltorphimine; D009271:Naltrexone; D001615:beta-Endorphin; C035581:beta-endorphin (1-27); C024524:beta-funaltrexamine