Identification of a β-arrestin-biased negative allosteric modulator for the β₂-adrenergic receptor.

ABSTRACT: Catecholamine-stimulated β₂-adrenergic receptor (β₂AR) signaling via the canonical G_s-adenylyl cyclase-cAMP-PKA pathway regulates numerous physiological functions, including the therapeutic effects of exogenous β-agonists in the treatment of airway disease. β₂AR signaling is tightly regulated by GRKs and β-arrestins, which together promote β₂AR desensitization and internalization as well as downstream signaling, often antithetical to the canonical pathway. Thus, the ability to bias β₂AR signaling toward the G_s pathway while avoiding β-arrestin-mediated effects may provide a strategy to improve the functional consequences of β₂AR activation. Since attempts to develop G_s-biased agonists

SUBMITTER: Ippolito M 

PROVIDER: S-EPMC10401000 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature