beta-funaltrexamine and rimorphin

It has been demonstrated that the antinociception induced by i.t. or i.c.v. administration of endomorphins is mediated through mu-opioid receptors. Moreover, though endomorphins do not have appreciable affinity for kappa-opioid receptors, pretreatment with the kappa-opioid receptor antagonist nor-binaltorphimine markedly blocks the antinociception induced by i.c.v.- or i.t.-injected endomorphin-2, but not endomorphin-1. These evidences propose the hypothesis that endomorphin-2 may initially stimulate the mu-opioid receptors, which subsequently induces the release of dynorphins acting on kappa-opioid receptors to produce antinociception. The present study was performed to determine whether the release of dynorphins by i.c.v.-administered endomorphin-2 is mediated through mu-opioid receptors for producing antinociception. Intracerebroventricular pretreatment with an antiserum against dynorphin A, but not dynorphin B or alpha-neo-endorphin, and s.c. pretreatment with kappa-opioid receptor antagonist nor-binaltorphimine dose-dependently attenuated the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1 and DAMGO. The attenuation of endomorphin-2-induced antinociception by pretreatment with antiserum against dynorphin A or nor-binaltorphimine was dose-dependently eliminated by additional s.c. pretreatment with a selective mu-opioid receptor antagonist beta-funaltrexamine or a selective mu1-opioid receptor antagonist naloxonazine at ultra low doses, which are inactive against micro-opioid receptor agonists in antinociception, suggesting that endomorphin-2 stimulates distinct subclass of micro1-opioid receptor that induces the release of dynorphin A acting on kappa-opioid receptors in the brain. It concludes that the antinociception induced by supraspinally administered endomorphin-2 is in part mediated through the release of endogenous kappa-opioid peptide dynorphin A, which is caused by the stimulation of distinct subclass of micro1-opioid receptor.

Topics: Analgesics; Animals; Dynorphins; Endorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Immune Sera; Injections, Intraventricular; Male; Mice; Naloxone; Naltrexone; Oligopeptides; Protein Precursors; Receptors, Opioid, kappa; Receptors, Opioid, mu

Dynorphin-A1-17 and dynorphin-B increased the evoked response of hippocampal CA1 pyramidal cells, as did other opioids tested. Treatment of the hippocampal slice with beta-funaltrexamine, a mu-receptor selective antagonist, blocked the effects of normorphine, dynorphin-A and dynorphin-B, but did not change the response to D-Ala2, D-Leu5-enkephalin. The low potency of kappa selective agonists and the antagonism by beta-funaltrexamine of the dynorphins' effect indicate that kappa-opioid receptors may not be involved in these observed responses. Our data suggest that both mu- and delta-receptors are functionally represented and provide evidence that the dynorphins or their derivatives may also be agonists at the mu-receptor.

Topics: Animals; Dynorphins; Endorphins; Hippocampus; In Vitro Techniques; Naltrexone; Rats; Receptors, Opioid; Receptors, Opioid, mu