ReferenceID 5096

A novel β2-AR agonist, Higenamine, induces β-arrestin-biased signaling

Sci China Life Sci

The biased ligands in G protein-coupled receptors (GPCRs) have opened new avenues for developing safer and more effective drugs. However, the identification of such biased ligands as drug candidates is highly desirable.

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Reference Id
5096
Evidence Id
21686
Core Evidence Id
21686
Source Reference Id
3481
Herb2 Reference Id
HBREF004278
Subject Paper Key
HBIN023239_34783996
Pubmed Id
34783996
Doi
10.1007/s11427-021-2008-1
Paper Title
A novel β2-AR agonist, Higenamine, induces β-arrestin-biased signaling
Paper Abstract
The biased ligands in G protein-coupled receptors (GPCRs) have opened new avenues for developing safer and more effective drugs. However, the identification of such biased ligands as drug candidates is highly desirable. Here, we report that Higenamine, a compound isolated from a Chinese herb, functions as a novel beta-arrestin-biased ligand of the beta2-adrenergic receptor (beta2-AR). The radioligand binding assays demonstrated that Higenamine was the ligand of beta2-AR. Higenamine induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), which can be blocked by propranolol, an inhibitor of beta2-AR. The Gi protein inhibitor, pertussis toxin, had no effect on the phosphorylation of ERK1/2 induced by Higenamine. Furthermore, Higenamine induced ERK1/2 phosphorylation through transactivation of Epithelial growth factor receptor (EGFR). We also found that Higenamine-induced-ERK1/2 phosphorylation is dependent on beta-arrestin1/2, and HG inhibits Doxorubicin-induced cardiomyocyte apoptosis. Our results identify Higenamine as a novel biased ligand via the beta-arrestin-dependent pathway. These findings give us a better understanding of Higenamine's potential role in designing diagnostic and therapeutic strategies.
Journal
Sci China Life Sci
Publish Year
2021
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
A novel β2-AR agonist, Higenamine, induces β-arrestin-biased signaling
Bilingual Status
semi_complete