Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor

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• dc.contributor.author Matthes, Hans W. D.ca
• dc.contributor.author Smadja, C.ca
• dc.contributor.author Valverde Granados, Olgaca
• dc.contributor.author Vonesch, J. L.ca
• dc.contributor.author Foutz, A. S.ca
• dc.contributor.author Boudinot, Elianeca
• dc.contributor.author Denavit-Saubié, M.ca
• dc.contributor.author Severini, Cintiaca
• dc.contributor.author Negri, Luciaca
• dc.contributor.author Roques, Bernard P.ca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Kieffer, Brigitte L.ca
• dc.date.accessioned 2012-07-05T06:54:26Z
• dc.date.available 2012-07-05T06:54:26Z
• dc.date.issued 1998ca
• dc.description.abstract Previous pharmacological studies have indicated the possible existence of functional interactions between μ-, δ- and κ-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of δ- and κ-opioid receptors in mice lacking the μ-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPγS binding and adenylyl cyclase inhibition showed that functional coupling of δ- and κ-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[d-penicillamine2,d-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR −/− mice. δ-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR −/− mice. Analgesic and respiratory responses produced by the selective κ-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of δ- and κ-receptor signaling properties in mice lacking μ-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the κ-agonist further suggest that the κ-receptor mainly acts independently from the μ-receptor in vivo. Reduced δ-analgesia and the absence of δ-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between μ-receptors and central δ-receptors in specific neuronal pathways.
• dc.description.sponsorship This work was f unded by institutional grants from C entre National de la Recherche Scientifique and Institut National de la Santé et de la Recherche Médicale and by specific grants from the Association pour la Recherche sur le Cancer, European Community Biomed-2 program, contract no. BM H4-C T96-0510. Institut Universitaire de France, Ministère de l’Education Nationale de l’Enseignement Supérieur et de la Recherche, Ministère de la Recherche et de la Technologie, and Fondation pour la Recherche Médicale.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Matthes HWD, Smadja C, Valverde O, Vonesch JL, Foutz AS, Boudinot E et al. Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor. J Neurosci. 1998;18(18):7285-95. DOI: 10.1523/jneurosci.18-18-07285.1998ca
• dc.identifier.doi http://dx.doi.org/10.1523/jneurosci.18-18-07285.1998
• dc.identifier.issn 0270-6474ca
• dc.identifier.uri http://hdl.handle.net/10230/16674
• dc.language.iso engca
• dc.publisher Society for Neuroscienceca
• dc.relation.ispartof Journal of Neuroscience. 1998;18(18):7285-95
• dc.rights © 1998, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/18/18/7285ca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword μ-opioid receptor knock-out
• dc.subject.keyword μ-δ-κ-opioid receptor interactions
• dc.subject.keyword G-protein coupling
• dc.subject.keyword δ-κ analgesia
• dc.subject.keyword Respiration
• dc.subject.keyword Vas deferens
• dc.subject.other Opiacis -- Receptors
• dc.subject.other Drogoaddicció -- Aspectes moleculars
• dc.title Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptorca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersion