δ-Opioid receptor agonists produce antinociception and [35S]GTPγS binding in μ receptor knockout mice

Yoshiaki Hosohata, Todd W. Vanderah, Thomas H. Burkey, Michael H. Ossipov, Carl J. Kovelowski, Ichiro Sora, George R. Uhl, Xiaoyan Zhang, Kenner C. Rice, William R. Roeske, Victor J. Hruby, Henry I. Yamamura, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

Abstract

We examined the effects of [D-Pen2,D-Pen5]enkephalin (DPDPE), [D- Ala2,Glu4]deltorphin (DELT), and (+)-4-[(αR)-α((2S,5R)-4-Allyl-2,5- dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) on [35S]GTPγS binding in brain membranes prepared from μ-opioid receptor knockout (-/-) mice. The potency and maximal response (E(max)) of these agonists were unchanged compared to control mice. In contrast, while the potency of [D-Pen2,pCl-Phe4,D-Pen5]enkephalin (pCl-DPDPE) was not significantly different, the E(max) was reduced as compared to controls. In the tail-flick test, intracerebroventricular (i.c.v.) or intrathecal (i.th.) DELT produced antinociceptive effects in -/- mice with potency that did not differ significantly from controls. In contrast, the antinociceptive potency of i.c.v. and i.th. DPDPE was displaced to the right by 4- and 9-fold in -/- compared to control mice, respectively. Reduced DPDPE antinociceptive potency in -/- mice, taken together with reduced DPDPE- and pCl-DPDPE- stimulated G protein activity in membranes prepared from -/- mice, demonstrate that these agonists require μ-opioid receptors for full activity. However, because DELT mediated G protein activation and antinociception were both comparable between -/- and wild type mice, we conclude that the μ-opioid receptor is not a critical component of δ-opioid receptor function. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalEuropean Journal of Pharmacology
Volume388
Issue number3
DOIs
Publication statusPublished - Feb 4 2000

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Keywords

  • δ-Opioid receptor
  • μ-Opioid receptor
  • μ-Opioid receptor-knockout mice
  • Antinociception
  • G protein
  • Opioid drug

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Hosohata, Y., Vanderah, T. W., Burkey, T. H., Ossipov, M. H., Kovelowski, C. J., Sora, I., ... Porreca, F. (2000). δ-Opioid receptor agonists produce antinociception and [35S]GTPγS binding in μ receptor knockout mice. European Journal of Pharmacology, 388(3), 241-248. https://doi.org/10.1016/S0014-2999(99)00897-3