Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aau2078 |
Genetic behavioral screen identifies an orphan anti-opioid system | |
Wang, Dandan1; Stoveken, Hannah M.1; Zucca, Stefano1; Dao, Maria1; Orlandi, Cesare1; Song, Chenghui1,4; Masuho, Ikuo1; Johnston, Caitlin1; Opperman, Karla J.1; Giles, Andrew C.1; Gill, Matthew S.2; Lundquist, Erik A.3; Grill, Brock1; Martemyanov, Kirill A.1 | |
2019-09-20 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6459页码:1267-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Opioids target the m-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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000487547400038 |
WOS关键词 | PROTEIN-COUPLED RECEPTORS ; RAT LOCUS-CERULEUS ; DESENSITIZATION ; PEPTIDES ; MORPHINE ; PAIN ; EXPRESSION ; ADDICTION ; TOLERANCE ; ANALGESIA |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202362 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA; 2.Scripps Res Inst, Dept Mol Med, Jupiter, FL 33458 USA; 3.Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA; 4.Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA |
推荐引用方式 GB/T 7714 | Wang, Dandan,Stoveken, Hannah M.,Zucca, Stefano,et al. Genetic behavioral screen identifies an orphan anti-opioid system[J]. SCIENCE,2019,365(6459):1267-+. |
APA | Wang, Dandan.,Stoveken, Hannah M..,Zucca, Stefano.,Dao, Maria.,Orlandi, Cesare.,...&Martemyanov, Kirill A..(2019).Genetic behavioral screen identifies an orphan anti-opioid system.SCIENCE,365(6459),1267-+. |
MLA | Wang, Dandan,et al."Genetic behavioral screen identifies an orphan anti-opioid system".SCIENCE 365.6459(2019):1267-+. |
条目包含的文件 | 条目无相关文件。 |
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