Autor: |
Thibaut Laboute, Jorge Gandía, Lucie P Pellissier, Yannick Corde, Florian Rebeillard, Maria Gallo, Christophe Gauthier, Audrey Léauté, Jorge Diaz, Anne Poupon, Brigitte L Kieffer, Julie Le Merrer, Jérôme AJ Becker |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
|
Zdroj: |
eLife, Vol 9 (2020) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.50519 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|