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 antinoc iceptive activity of i.c.v. administered beta-endorphin in mice. In th is study the antagonist activity of beta-endorphin(1-27) has been conf irmed and the antagonism appears to be mediated at delta1 opioid recep tors. At higher doses than that used for antagonism, i.c.v. administer ed beta-endorphin(1-27) was a full antinociceptive agonist. The antino ciceptive activity of beta-endorphin is attributed to the release of m et-enkephalin in the spinal cord and is antagonized by the selective d elta2 opioid receptor antagonist, naltriben (NTB) but not by the selec tive delta1 opioid receptor antagonist, 7-benzylidenenaltrexone (BNTX) . In contrast, the antinociceptive activity of i.c.v. administered bet a-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(I- 27) was unaffected by the selective mu opioid receptor antagonist, bet a-funaltrexamine (beta-FNA) or the selective kappa opioid receptor ant agonist, norbinaltorphimine (norBNI). Thus, beta-endorphin(1-27) appea rs to mediate antinociception supraspinally through the interaction of a unique receptor, i.e. a receptor that is different from mu, kappa, delta1 or delta2 opioid receptors. Alternatively, a non-opioid mechani sm may be considered.