beta-endorphin-(1-27) and 7-benzylidenenaltrexone

The effect of derivatives of beta-endorphin on the contractile response to indirect stimulation in mouse diaphragm muscle was studied to determine whether the action of the peptide to increase muscle tension is an opioid effect. beta-Endorphin (1-27), beta-endorphin (30-31), and a beta-endorphin (28-31) analogue all increased the amplitude of the contractions. The C-terminal peptides were more potent than beta-endorphin or beta-endorphin (1-27). The beta-endorphin (28-31) analogue, like beta-endorphin, decreased the time to peak but beta-endorphin (1-27) did not. The effect of beta-endorphin (1-27), but not that of the beta-endorphin (28-31) analogue, was blocked by naloxone. Thus, beta-endorphin acts on muscle via both opioid and nonopioid receptors.

Topics: Animals; Benzylidene Compounds; beta-Endorphin; Diaphragm; Dipeptides; Electric Stimulation; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Female; Mice; Mice, Inbred C57BL; Muscle Contraction; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Neostigmine; Oligopeptides; Peptide Fragments

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.

Topics: Animals; Benzylidene Compounds; beta-Endorphin; Male; Mice; Naltrexone; Narcotic Antagonists; Nociceptors; Peptide Fragments; Receptors, Opioid