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Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor
Matthes, Hans W. D.; Smadja, C.; Valverde, Olga; Vonesch, J. L.; Foutz, A. S.; Boudinot, E.; Denavit-Saubié, M.; Severini, Cintia; Negri, Lucia; Roques, B. P.; Maldonado, Rafael; Kieffer, Brigitte L.
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.
02-07-2013
Opiacis -- Receptors
Drogoaddicció -- Aspectes moleculars
μ-opioid receptor knock-out
μ-δ-κ-opioid receptor interactions
G-protein coupling
δ-κ analgesia
Respiration
Vas deferens
(c) 1998, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/18/18/7285
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info:eu-repo/semantics/publishedVersion
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