Matthes, Hans W. D.Smadja, C.Valverde Granados, OlgaVonesch, J. L.Foutz, A. S.Boudinot, ElianeDenavit-Saubié, M.Severini, CintiaNegri, LuciaRoques, Bernard P.Maldonado, Rafael, 1961-Kieffer, Brigitte L.2012-07-052012-07-051998Matthes 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.18-18-07285.19980270-6474http://hdl.handle.net/10230/16674Previous 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.application/pdfeng© 1998, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/18/18/7285Opiacis -- ReceptorsDrogoaddicció -- Aspectes molecularsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1523/jneurosci.18-18-07285.1998μ-opioid receptor knock-outμ-δ-κ-opioid receptor interactionsG-protein couplingδ-κ analgesiaRespirationVas deferensinfo:eu-repo/semantics/openAccess