TY - JOUR T1 - μ-Opioid Receptors: Correlation of Agonist Efficacy for Signalling with Ability to Activate Internalization JF - Molecular Pharmacology JO - Mol Pharmacol SP - 756 LP - 766 DO - 10.1124/mol.110.066613 VL - 78 IS - 4 AU - Jamie McPherson AU - Guadalupe Rivero AU - Myma Baptist AU - Javier Llorente AU - Suleiman Al-Sabah AU - Cornelius Krasel AU - William L. Dewey AU - Chris P. Bailey AU - Elizabeth M. Rosethorne AU - Steven J. Charlton AU - Graeme Henderson AU - Eamonn Kelly Y1 - 2010/10/01 UR - http://molpharm.aspetjournals.org/content/78/4/756.abstract N2 - We have compared the ability of a number of μ-opioid receptor (MOPr) ligands to activate G proteins with their abilities to induce MOPr phosphorylation, to promote association of arrestin-3 and to cause MOPr internalization. For a model of G protein-coupled receptor (GPCR) activation where all agonists stabilize a single active conformation of the receptor, a close correlation between signaling outputs might be expected. Our results show that overall there is a very good correlation between efficacy for G protein activation and arrestin-3 recruitment, whereas a few agonists, in particular endomorphins 1 and 2, display apparent bias toward arrestin recruitment. The agonist-induced phosphorylation of MOPr at Ser375, considered a key step in MOPr regulation, and agonist-induced internalization of MOPr were each found to correlate well with arrestin-3 recruitment. These data indicate that for the majority of MOPr agonists the ability to induce receptor phosphorylation, arrestin-3 recruitment, and internalization can be predicted from their ability as agonists to activate G proteins. For the prototypic MOPr agonist morphine, its relatively weak ability to induce MOPr internalization can be explained by its low agonist efficacy. ER -