| First Author | Laboute T | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32003745 | Mgi Jnum | J:292428 |
| Mgi Id | MGI:6442988 | Doi | 10.7554/eLife.50519 |
| Citation | Laboute T, et al. (2020) The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs. Elife 9:e50519 |
| abstractText | 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 beta-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 microOR 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 beta-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. |
