Modulation of Mu-mediated antinociception in the mouse involves opioid delta-2 receptors

F. Porreca, A. E. Takemori, M. Sultana, P. S. Portoghese, W. D. Bowen, H. I. Mosberg

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Abstract

Recently, subtypes of the opioid δ receptor have been identified. It is not known, however, if a subtype of opioid δ receptor can be associated with the known modulatory action of δ agonists on μ-mediated antinociception. Thus, the present study has used the δ subtype-selective antagonists, [D- Ala2,Leu5,Cys6]enkephalin (DALCE) (δ1 antagonist) and naltrindole-5'- isothiocyanate (5'-NTII) (δ2 antagonist) in an effort to determine whether the positive and negative modulation of morphine antinociception produced by opioid δ agonists was the result of activity at specific subtypes of opioid δ receptors. Intracerebroventricular morphine produced a dose-related antinociceptive effect which was not antagonized by coadministration of the δ antagonist, ICI 174,864, or by pretreatment 24 hr before testing with the DALCE or 5'-NTII. Coadministration with morphine of a nonantinociceptive dose of DPDPE or [D-Ala2,Glu4]deltorphin resulted in a leftward displacement of the morphine dose-effect curve (i.e., positive modulation), whereas coadministration of a nonantinociceptive dose of [Met5]enkephalin with morphine resulted in a rightward displacement of the morphine dose-effect curve (i.e., negative modulation). Both the positive and the negative modulatory actions were antagonized when the experiment was conducted in the presence of the δ antagonist, ICI 174,864, or when the mice were pretreated with the δ2 antagonist, 5'-NTII. In contrast, pretreatment with the δ1- antagonist, DALCE, failed to affect either the positive or the negative modulatory actions of these δ agonists on morphine antinociception. The data suggest the involvement of an opioid δ2 receptor in the modulation of morphine antinociception.

Original languageEnglish (US)
Pages (from-to)147-152
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number1
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Porreca, F., Takemori, A. E., Sultana, M., Portoghese, P. S., Bowen, W. D., & Mosberg, H. I. (1992). Modulation of Mu-mediated antinociception in the mouse involves opioid delta-2 receptors. Journal of Pharmacology and Experimental Therapeutics, 263(1), 147-152.