μ-Opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization

Jamie L McPherson, Guadalupe Rivero, Myma C Baptist, F J Llorente, Suleiman Al-Sabah, Cornelius Krasel, William L Dewey, CP Bailey, Elizabeth M Rosethorne, Steven J Charlton, G Henderson, E Kelly

Research output: Contribution to journalArticle (Academic Journal)peer-review

182 Citations (Scopus)

Abstract

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 Ser(375), 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.
Translated title of the contributionμ-Opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization
Original languageEnglish
Pages (from-to)756 - 766
Number of pages11
JournalMolecular Pharmacology
Volume78
Issue number4
DOIs
Publication statusPublished - Oct 2010

Bibliographical note

Author of Publication Reviewed: J McPherson, G Rivero, M Baptist, J Llorente, S Al-Sabah, C Krasel, WL Dewey, CP Bailey, EM Rosethorne, SJ Charlton, G Henderson & E Kelly
Publisher: HighWire

Fingerprint Dive into the research topics of 'μ-Opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization'. Together they form a unique fingerprint.

Cite this