Recruitment of β-arrestin 1 and 2 to the β2-adrenoceptor: analysis of 65 ligands.

ABSTRACT:

Unlabelled

Beyond canonical signaling via Gαs and cAMP, the concept of functional selectivity at β2-adrenoceptors (β2ARs) describes the ability of adrenergic drugs to stabilize ligand-specific receptor conformations to initiate further signaling cascades comprising additional G-protein classes or β-arrestins (βarr). A set of 65 adrenergic ligands including 40 agonists and 25 antagonists in either racemic or enantiopure forms was used for βarr recruitment experiments based on a split-luciferase assay in a cellular system expressing β2AR. Many agonists showed only (weak) partial agonism regarding βarr recruitment. Potencies and/or efficacies increased depending on the number of chirality centers in (R) configuration; no (S)-configured distomer was more effective at inducing βarr recr

SUBMITTER: Littmann T 

PROVIDER: S-EPMC4631950 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature