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

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

Research output: Contribution to journalArticle

104 Citations (Scopus)

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 - 1992

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delta Opioid Receptor
Morphine
Enkephalins
Opioid Receptors
D-Penicillamine (2,5)-Enkephalin
Opioid Analgesics

ASJC Scopus subject areas

  • 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.

Modulation of Mu-mediated antinociception in the mouse involves opioid delta-2 receptors. / Porreca, Frank; Takemori, A. E.; Sultana, M.; Portoghese, P. S.; Bowen, W. D.; Mosberg, H. I.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 263, No. 1, 1992, p. 147-152.

Research output: Contribution to journalArticle

Porreca, F, Takemori, AE, Sultana, M, Portoghese, PS, Bowen, WD & Mosberg, HI 1992, 'Modulation of Mu-mediated antinociception in the mouse involves opioid delta-2 receptors', Journal of Pharmacology and Experimental Therapeutics, vol. 263, no. 1, pp. 147-152.
Porreca, Frank ; Takemori, A. E. ; Sultana, M. ; Portoghese, P. S. ; Bowen, W. D. ; Mosberg, H. I. / Modulation of Mu-mediated antinociception in the mouse involves opioid delta-2 receptors. In: Journal of Pharmacology and Experimental Therapeutics. 1992 ; Vol. 263, No. 1. pp. 147-152.
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