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  • Title: [Met]enkephalin in the spinal cord is involved in the antinociception induced by intracerebroventricularly-administered etorphine in the mouse.
    Author: Xu JY, Tseng LF.
    Journal: Neuroscience; 1997 Sep; 80(2):579-85. PubMed ID: 9284359.
    Abstract:
    We have recently reported that the antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of both mu- and epsilon-opioid receptors and the activation of both monoaminergic and opioidergic descending pain control systems. [Xu J. Y. et al. (1992) J. Pharmac. exp. Ther. 263, 246-252]. Since the opioid epsilon-receptor-mediated antinociception induced by beta-endorphin is mediated by the release of [Met]enkephalin and subsequent stimulation of delta-opioid receptors in the spinal cord, the present studies were designed to determine if beta-endorphin-like action is also involved in etorphine-induced antinociception. The tail-flick test was used to assess the antinociceptive response performed in male ICR mice. Etorphine at doses from 5 to 20 ng given i.c.v. produced a dose-dependent inhibition of the tail-flick response. The inhibition of the tail-flick response induced by etorphine given i.c.v. was antagonized by intrathecal pretreatment for 60 min with antiserum against [Met]enkephalin (10 microg), but not with antiserum against [Leu]enkephalin (10 microg) or dynorphin A (1-13) (10 microg). Desensitization of delta-opioid receptors in the spinal cord by intrathecal pretreatment with [Met]enkephalin (5 microg) for 60 min attenuated i.c.v. administered etorphine-induced tail-flick inhibition. However, intrathecal pretreatment with [Leu]enkephalin (5 microg) or dynorphin A (1-17) (0.1 microg) for 60 min did not attenuate i.c.v. administered etorphine-induced tail-flick inhibition. The results indicate that antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of the epsilon-opioid receptor at the supraspinal sites and by the release of [Met]enkephalin, which subsequently stimulates delta-opioid receptors in the spinal cord.
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