ß-adrenergic receptor signaling mediated by ß-arrestins and its potential role in heart failure.
Curr Opin Physiol
; 372024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38094036
ABSTRACT
The lethality of heart failure (HF), particularly in the context of post-acute sequelae SARS-CoV-2 infection (PASC)-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease (CVD). We summarize the signaling mechanisms of the catecholamine-binding ß-adrenergic receptors (ß-ARs), with an emphasis on the role of ß-arrestins. ß-ARs, a subset of G protein-coupled receptors (GPCRs), canonically propagate signals through heterotrimeric G proteins. However, since their discovery in the late 1980s, ß-arrestins have been shown to, both (i) quench G protein signaling and (ii) initiate their own independent signaling cascades, which is influenced by post-translational modifications. ß-arrestin-biased agonism by the beta-blocker carvedilol and its allosteric modulation can serve a cardioprotective role. The increasingly labyrinthine nature of GPCR signaling suggests that ligand-dependent ß-AR signaling, either stimulated by an agonist or blocked by an antagonist, is selectively enhanced or suppressed by allosteric modulations, which are orchestrated by novel drugs or endogenous post-translational modifications.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Curr Opin Physiol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos