G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists.

ABSTRACT: The ability of a ligand to preferentially promote engagement of one signaling pathway over another downstream of GPCR activation has been referred to as signaling bias, functional selectivity, and biased agonism. The presentation of ligand bias reflects selectivity between active states of the receptor, which may result in the display of preferential engagement with one signaling pathway over another. In this study, we provide evidence that the G protein-biased mu opioid receptor (MOR) agonists SR-17018 and SR-14968 stabilize the MOR in a wash-resistant yet antagonist-reversible G protein-signaling state. Furthermore, we demonstrate that these structurally related biased agonists are noncompetitive for radiolabeled MOR antagonist binding, and while they stimulate G protein signaling in mou

SUBMITTER: Stahl EL 

PROVIDER: S-EPMC8640941 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature