| First Author | Wang D | Year | 2019 |
| Journal | Science | Volume | 365 |
| Issue | 6459 | Pages | 1267-1273 |
| PubMed ID | 31416932 | Mgi Jnum | J:280704 |
| Mgi Id | MGI:6369477 | Doi | 10.1126/science.aau2078 |
| Citation | Wang D, et al. (2019) Genetic behavioral screen identifies an orphan anti-opioid system. Science 365(6459):1267-1273 |
| abstractText | Opioids target the mu-opioid receptor (MOR) to produce unrivaled pain management, but their addictive properties can lead to severe abuse. We developed a whole-animal behavioral platform for unbiased discovery of genes influencing opioid responsiveness. Using forward genetics in Caenorhabditis elegans, we identified a conserved orphan receptor, GPR139, with anti-opioid activity. GPR139 is coexpressed with MOR in opioid-sensitive brain circuits, binds to MOR, and inhibits signaling to heterotrimeric guanine nucleotide-binding proteins (G proteins). Deletion of GPR139 in mice enhanced opioid-induced inhibition of neuronal firing to modulate morphine-induced analgesia, reward, and withdrawal. Thus, GPR139 could be a useful target for increasing opioid safety. These results also demonstrate the potential of C. elegans as a scalable platform for genetic discovery of G protein-coupled receptor signaling principles. |
