ReviewBritish journal of pharmacology2015
Biased β2-adrenoceptor signalling in heart failure: pathophysiology and drug discovery.
Review in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 72 citations in OpenAlex.
- Age-dependent Transcriptional Programs Distinguish Pediatric from Adult Dilated Cardiomyopathy.medRxiv : the preprint server for health sciences · 2026Article
- Biased Agonism at β-Adrenoceptor Subtypes: A Drug Development Perspective.Handbook of experimental pharmacology · 2026Review
- The beta1-adrenergic receptor in the heart.Cell death discovery · 2025Review
- Implication of Central βArchiv der Pharmazie · 2025Review
- Structure and dynamics determine G protein coupling specificity at a class A GPCR.Science advances · 2025Article
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders.Handbook of experimental pharmacology · 2024Review
- Association among β2-adrenergic receptor autoantibodies and proximal left anterior descending artery lesions in patients with initial ST-segment elevation myocardial infarction.Clinical cardiology · 2023Article
- Status of βReviews in cardiovascular medicine · 2023Review
- Adrenoceptor sub-type involvement in CaPflugers Archiv : European journal of physiology · 2022Article
- QR code model: a new possibility for GPCR phosphorylation recognition.Cell communication and signaling : CCS · 2022Review
- Identification of novel biomarkers involved in doxorubicin-induced acute and chronic cardiotoxicity, respectively, by integrated bioinformatics.Frontiers in cardiovascular medicine · 2022Article
- Biased activation of βCell death discovery · 2021Article
- Amino terminal recognition by a CCR6 chemokine receptor antibody blocks CCL20 signaling and IL-17 expression via β-arrestin.BMC biotechnology · 2021Article
- Review
- Upregulation of βNaunyn-Schmiedeberg's archives of pharmacology · 2020Review
- Androgen Effects on the Adrenergic System of the Vascular, Airway, and Cardiac Myocytes and Their Relevance in Pathological Processes.International journal of endocrinology · 2020Review
- Discovery of β-arrestin-biased βActa pharmacologica Sinica · 2019Article
- Adrenoceptor regulation of the mechanistic target of rapamycin in muscle and adipose tissue.British journal of pharmacology · 2019Review
- Cardiac βBritish journal of pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The body is constantly faced with a dynamic requirement for blood flow. The heart is able to respond to these changing needs by adjusting cardiac output based on cues emitted by circulating catecholamine levels. Cardiac β-adrenoceptors transduce the signal produced by catecholamine stimulation via Gs proteins to their downstream effectors to increase heart contractility. During heart failure, cardiac output is insufficient to meet the needs of the body; catecholamine levels are high and β-adrenoceptors become hyperstimulated. The hyperstimulated β1-adrenoceptors induce a cardiotoxic effect, which could be counteracted by the cardioprotective effect of β2-adrenoceptor-mediated Gi signalling. However, β2-adrenoceptor-Gi signalling negates the stimulatory effect of the Gs signalling on cardiomyocyte contraction and further exacerbates cardiodepression. Here, further to the localization of β1- and β2-adrenoceptors and β2-adrenoceptor-mediated β-arrestin signalling in cardiomyocytes, we discuss features of the dysregulation of β-adrenoceptor subtype signalling in the failing heart, and conclude that Gi-biased β2-adrenoceptor signalling is a pathogenic pathway in heart failure that plays a crucial role in cardiac remodelling. In contrast, β2-adrenoceptor-Gs signalling increases cardiomyocyte contractility without causing cardiotoxicity. Finally, we discuss a novel therapeutic approach for heart failure using a Gs-biased β2-adrenoceptor agonist and a β1-adrenoceptor antagonist in combination. This combination treatment normalizes the β-adrenoceptor subtype signalling in the failing heart and produces therapeutic effects that outperform traditional heart failure therapies in animal models. The present review illustrates how the concept of biased signalling can be applied to increase our understanding of the pathophysiology of diseases and in the development of novel therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.