PT - JOURNAL ARTICLE AU - Peilan Zhou AU - Jiebing Jiang AU - Hui Yan AU - Yulei Li AU - Junru Zhao AU - Xiao Wang AU - Ruibin Su AU - Zehui Gong TI - ABIN-1 Negatively Regulates <em>μ</em>-Opioid Receptor Function AID - 10.1124/mol.117.109009 DP - 2018 Feb 01 TA - Molecular Pharmacology PG - 36--48 VI - 93 IP - 2 4099 - http://molpharm.aspetjournals.org/content/93/2/36.short 4100 - http://molpharm.aspetjournals.org/content/93/2/36.full SO - Mol Pharmacol2018 Feb 01; 93 AB - The μ-opioid receptor (MOR) is a Gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. Using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat MOR associates with A20-binding inhibitor of nuclear factor κB (ABIN-1). This interaction was confirmed by direct protein-protein binding and coimmunoprecipitation of MOR and ABIN-1 proteins in cell lysates. Saturation binding studies showed that ABIN-1 had no effect on MOR binding. However, the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin). MOR phosphorylation, ubiquitination, and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1. The suppression of forskolin-stimulated adenylyl cyclase by DAMGO was also inhibited by the interaction of ABIN-1 with MOR. In addition, extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1. These data suggest that ABIN-1 is a negative coregulator of MOR activation, phosphorylation, and internalization in vitro. ABIN-1 also inhibited morphine-induced hyperlocomotion in zebrafish larvae (AB strain). By utilization of an antisense morpholino oligonucleotide (MO) gene knockdown technology, the ABIN-1 MO-injected zebrafish larvae showed a significant increase (approximately 60%) in distance moved compared with control MO-injected larvae after acute morphine treatment (P &lt; 0.01). Taken together, ABIN-1 negatively regulates MOR function in vitro and in vivo.