دورية أكاديمية
The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs
| العنوان: | The orphan receptor GPR88 blunts the signaling of opioid receptors and multiple striatal GPCRs |
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| المؤلفون: | 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 |
| المصدر: | eLife, Vol 9 (2020) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | in vitro pharmacology, BRET experiments, beta-arrestin, GPCR oligomerisation, knockout animals, in vivo pharmacology, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/50519Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.50519 |
| الوصول الحر: | https://doaj.org/article/68fc1b1b72044d1da177f37a7c4ff79fTest |
| رقم الانضمام: | edsdoj.68fc1b1b72044d1da177f37a7c4ff79f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.50519 |