| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2008271 | Peptides | 2008 | 7 Pages |
It has been demonstrated that the antinociception induced by i.t. or i.c.v. administration of endomorphins is mediated through μ-opioid receptors. Moreover, though endomorphins do not have appreciable affinity for κ-opioid receptors, pretreatment with the κ-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 μ-opioid receptors, which subsequently induces the release of dynorphins acting on κ-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 μ-opioid receptors for producing antinociception. Intracerebroventricular pretreatment with an antiserum against dynorphin A, but not dynorphin B or α-neo-endorphin, and s.c. pretreatment with κ-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 μ-opioid receptor antagonist β-funaltrexamine or a selective μ1-opioid receptor antagonist naloxonazine at ultra low doses, which are inactive against μ-opioid receptor agonists in antinociception, suggesting that endomorphin-2 stimulates distinct subclass of μ1-opioid receptor that induces the release of dynorphin A acting on κ-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 κ-opioid peptide dynorphin A, which is caused by the stimulation of distinct subclass of μ1-opioid receptor.
