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

A. E. Takemori, P. S. Portoghese

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46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalEuropean Journal of Pharmacology
Volume242
Issue number2
DOIs
StatePublished - Sep 28 1993

Bibliographical note

Funding Information:
Correspondence to: A.E. Takemori, Department of Pharmacology, 3-249 Millard Hall, University of Minnesota, 435 Delaware Street S.E., Minneapolis, MN 55455, USA. * This investigation was supported by U.S. Public Health Service grants from the National Institute on Drug Abuse. Studies in this report were carried out in accordance with the Declaration of Helsinki and/or with the guide for the care and use of laboratory animals as adopted and promulgated by the National Institutes of Health.

Keywords

  • Antinociception
  • BNTX (7-benzylidenenaltrexone)
  • Brain
  • Naltriben
  • Spinal cord
  • [Leu]enkephalin
  • [Met]enkephalin
  • β-Endorphin
  • δ-Opioid receptors
  • δ-Opioid receptors

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