S-nitrosylation is required for β₂AR desensitization and experimental asthma.

ABSTRACT: The β₂-adrenergic receptor (β₂AR), a prototypic G-protein-coupled receptor (GPCR), is a powerful driver of bronchorelaxation, but the effectiveness of β-agonist drugs in asthma is limited by desensitization and tachyphylaxis. We find that during activation, the β₂AR is modified by S-nitrosylation, which is essential for both classic desensitization by PKA as well as desensitization of NO-based signaling that mediates bronchorelaxation. Strikingly, S-nitrosylation alone can drive β₂AR internalization in the absence of traditional agonist. Mutant β₂AR refractory to S-nitrosylation (Cys265Ser) exhibits reduced desensitization and internalization, thereby amplifying NO-based signaling, and mice with Cys265Ser mutation are resistant to bron

SUBMITTER: Fonseca FV 

PROVIDER: S-EPMC9391322 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature