Elsevier

European Journal of Pharmacology

Volume 242, Issue 2, 28 September 1993, Pages 145-150
European Journal of Pharmacology

Enkephalin antinociception in mice is mediated by δ1- and δ2-opioid receptors in the brain and spinal cord, respectively

https://doi.org/10.1016/0014-2999(93)90074-RGet rights and content

Abstract

Pharmacological evidence for the existence of δ-opioid receptor subtypes has been reported. This study was conducted to determine which type of δ-opioid receptors was involved supraspinally and spinally when antinociception was induced by the natural enkephalins, [Leu5]enkephalin and [Met5]enkephalin. In the mouse tail flick assay, the antinociceptive ED50 values of both intracerebroventricularly (i.c.v.) administered [Leu5]enkephalin and [Met5]enkephalin (together with the peptidase inhibitors, bestatin and thiorphan) were significantly increased by 7-benzylidenenaltrexone (BNTX), a selective δ1-opioid receptor antagonist but not by naltriben, a selective δ2-opioid receptor antagonist. On the other hand, when the enkephalins were administered intrathecally (i.t.), the antinociceptive ED50 values of both enkephalins were significantly raised by naltriben but not by BNTX. β-Endorphin-induced (i.c.v.) antinociception was antagonized by naltriben administered i.t. or s.c. but not by BNTX administered i.t. or s.c. Different δ-opioid receptor subtypes appeared to be involved in supraspinal (δ1) and spinal (δ2) antinociception induced by endogenous δ-opioid receptor agonists, [Leu5] and [Met5]enkephalin. The antinociception produced by i.c.v. administered β-endorphin has been attributed to the release of [Met5]enkephalin in the spinal cord and its antagonism by naltriben support the finding that enkephalins interact with δ2-opioid receptors in the spinal cord to mediate antinociception. β-Endorphin may be interacting at receptors other than δ1-or δ2-opioid receptors in the brain, perhaps the putative ε receptors, to mediate their effects because neither i.c.v. administered BNTX nor naltriben inhibited its activity.

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