The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs.

Autor:	Laboute T; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France., Gandía J; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France., Pellissier LP; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France.; Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France., Corde Y; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France., Rebeillard F; Cellular Biology and Molecular Pharmacology of central Receptors, Centre de Psychiatrie et Neurosciences, Inserm UMR_S894 - Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Gallo M; Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Barcelona, Spain., Gauthier C; Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France., Léauté A; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France., Diaz J; Cellular Biology and Molecular Pharmacology of central Receptors, Centre de Psychiatrie et Neurosciences, Inserm UMR_S894 - Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Poupon A; Biology and Bioinformatics of Signalling Systems, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Nouzilly, France., Kieffer BL; Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France., Le Merrer J; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France.; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France., Becker JA; Deficits of Reward GPCRs and Sociability, Physiologie de la Reproduction et des Comportements, INRA UMR-0085, CNRS UMR-7247, Université de Tours, Inserm, Nouzilly, France.; Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, Inserm U1258, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Jan 31; Vol. 9. Date of Electronic Publication: 2020 Jan 31.
DOI:	10.7554/eLife.50519
Abstrakt:	GPR88 is an orphan G protein-coupled receptor (GPCR) considered as a promising therapeutic target for neuropsychiatric disorders; its pharmacology, however, remains scarcely understood. Based on our previous report of increased delta opioid receptor activity in Gpr88 null mice, we investigated the impact of GPR88 co-expression on the signaling of opioid receptors in vitro and revealed that GPR88 inhibits the activation of both their G protein- and β-arrestin-dependent signaling pathways. In Gpr88 knockout mice, morphine-induced locomotor sensitization, withdrawal and supra-spinal analgesia were facilitated, consistent with a tonic inhibitory action of GPR88 on µOR signaling. We then explored GPR88 interactions with more striatal versus non-neuronal GPCRs, and revealed that GPR88 can decrease the G protein-dependent signaling of most receptors in close proximity, but impedes β-arrestin recruitment by all receptors tested. Our study unravels an unsuspected buffering role of GPR88 expression on GPCR signaling, with intriguing consequences for opioid and striatal functions. Competing Interests: TL, JG, LP, YC, FR, MG, CG, AL, JD, AP, BK, JL, JB No competing interests declared (© 2020, Laboute et al.)
Databáze:	MEDLINE
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