IJDDP/
Articles/
2504000135
  • Open Access
  • Review
Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease
  • Ying Song 1,   
  • Anthony Yiu-Ho WOO 2, *,   
  • Yan Zhang 3, 4, *,   
  • Ruiping Xiao 5, 6, 7, 8

Received: 19 Oct 2022 | Accepted: 28 Nov 2022 | Published: 21 Dec 2022

Abstract

A variety of G protein-coupled receptors (GPCRs) are involved in the regulation of cardiovascular function. The β-adrenoceptors (β-ARs), with three subtypes, are the dominant receptor species in the heart, in which the β1-AR and the β2-AR are considered functional. Stimulation of the β-ARs produces myocardial inotropy via activation of the Gs-cAMP-PKA signaling cascade. Prolonged stimulation of the β1-AR is cardiac harmful because the stimulated β1-AR couples only to Gs proteins and it mediates a cardiotoxic signal. On the other hand, the β2-AR couples dually to both Gs and Gi proteins and the β2-AR-Gi pathway is antiapoptotic. The activated Gi signal also counteracts the β-AR-Gs-promoted positive inotropic effect. Other key players in cardiac β-AR signaling include Ca2+/calmodulin-dependent protein kinases (CaMKs), GPCR kinases (GRKs), β-arrestins and phosphodiesterases. During heart failure, excessive sympathetic stimulation results in the activation of the cardiotoxic β1-AR-CaMKIIδ pathway and the upregulation of GRK2 and Gi in the heart. GRK2 promotes the desensitization of β-ARs and enhances a β2-AR-mediated Gi signaling. These signal transduction processes accompanying the downregulation of the β1-AR are involved in cardiac dysfunction, maladaptive cardiac remodeling, and the progression of chronic heart failure. β-Blockers are widely used in the treatment of cardiovascular disease. They have established their position as one of the “four pillars of heart failure” thirty years ago. In the present review, we provide an overview of the recent progress in the basic research of GPCRs focusing on cardiac β-AR signal transduction.

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10.53941/ijddp.v1i1.177
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Volume 1, Issue 1
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Song, Y.; WOO, A. Y.-H.; Zhang, Y.; Xiao, R. Cardiac β-Adrenoceptor Signaling: The New Insight on An Old Target in the Therapy of Cardiovascular Disease. International Journal of Drug Discovery and Pharmacology 2022, 1 (1), 3. https://doi.org/10.53941/ijddp.v1i1.177.
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Ying Song, Anthony Yiu-Ho WOO, Yan ZHANG, Rui-Ping Xiao