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Papers of the Week

Papers: 1 Feb 2020 - 7 Feb 2020

Animal Studies, Pharmacology/Drug Development

2020 01 31



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


Laboute T, Gandía J, Pellissier LP, Corde Y, Rebeillard F, Gallo M, Gauthier C, Léauté A, Diaz J, Poupon A, Kieffer BL, Le Merrer J, Becker JAJ
Elife. 2020 01 31; 9.
PMID: 32003745.


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 null mice, we investigated the impact of GPR88 co-expression on the signaling of opioid receptors and revealed that GPR88 inhibits the activation of both their G protein- and b-arrestin-dependent signaling pathways. In 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 b-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.