Functional selectivity of EM-2 analogs at the mu-opioid receptor

ABSTRACT: The mu opioid receptor agonists are the most efficacious pain controlling agents but their use is accompanied by severe side effects. More recent developments indicate that some ligands can differentially activate receptor downstream pathways, possibly allowing for dissociation of analgesia mediated through the G protein from the opioid-related side effects mediated by β-arrestin pathway. In an effort to identify such biased ligands, here we present a series of thirteen endomorphin-2 (EM-2) analogs with modifications in positions 1, 2, and/or 3. All obtained analogs behaved as mu receptor selective agonists in calcium mobilization assay carried out on cells expressing opioid receptors and chimeric G proteins. A Bioluminescence Resonance Energy Transfer (BRET) approach was employed to deter

SUBMITTER: Piekielna-Ciesielska J 

PROVIDER: S-EPMC9998502 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature