ArticleBiochemical pharmacology2014
Probing biased/partial agonism at the G protein-coupled A(2B) adenosine receptor.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2026Review
- APurinergic signalling · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- APurinergic signalling · 2025Review
- MRS3997, a dual adenosine ANeuropharmacology · 2025Article
- A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C.Research square · 2024Article
- Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis.Journal of cachexia, sarcopenia and muscle · 2024Article
- New paradigms in purinergic receptor ligand discovery.Neuropharmacology · 2023Review
- Cryo-EM structure of the human adenosine AScience advances · 2022Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B.International journal of molecular sciences · 2021Article
- Role of Adenosine and Purinergic Receptors in Myocardial Infarction: Focus on Different Signal Transduction Pathways.Biomedicines · 2021Review
- Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on AFrontiers in pharmacology · 2021Article
- Design and in vivo activity of APurinergic signalling · 2020Article
- Review
- AInternational journal of molecular sciences · 2019Review
- Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development.Frontiers in cellular neuroscience · 2019Review
- Probing structure-activity relationship in β-arrestin2 recruitment of diversely substituted adenosine derivatives.Biochemical pharmacology · 2018Article
- New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism.British journal of pharmacology · 2018Review
- Tritium-labeled agonists as tools for studying adenosine APurinergic signalling · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled A(2B) adenosine receptor (AR) regulates numerous important physiological functions, but its activation by diverse A(2B)AR agonists is poorly profiled. We probed potential partial and/or biased agonism in cell lines expressing variable levels of endogenous or recombinant A(2B)AR. In cAMP accumulation assays, both 5'-substituted NECA and C2-substituted MRS3997 are full agonists. However, only 5'-substituted adenosine analogs are full agonists in calcium mobilization, ERK1/2 phosphorylation and β-arrestin translocation. A(2B)AR overexpression in HEK293 cells markedly increased the agonist potency and maximum effect in cAMP accumulation, but less in calcium and ERK1/2. A(2B)AR siRNA silencing was more effective in reducing the maximum cAMP effect of non-nucleoside agonist BAY60-6583 than NECA's. A quantitative 'operational model' characterized C2-substituted MRS3997 as either balanced (cAMP accumulation, ERK1/2) or strongly biased agonist (against calcium, β-arrestin). N⁶-substitution biased against ERK1/2 (weakly) and calcium and β-arrestin (strongly) pathways. BAY60-6583 is ERK1/2-biased, suggesting a mechanism distinct from adenosine derivatives. BAY60-6583, as A(2B)AR antagonist in MIN-6 mouse pancreatic β cells expressing low A(2B)AR levels, induced insulin release. This is the first relatively systematic study of structure-efficacy relationships of this emerging drug target.
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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.