ArticleThe Journal of pharmacology and experimental therapeutics2011
A role for the low-affinity A2B adenosine receptor in regulating superoxide generation by murine neutrophils.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- MRS3997, a dual adenosine ANeuropharmacology · 2025Article
- Adenosine-mediated immune responses in inflammatory bowel disease.Frontiers in cell and developmental biology · 2024Review
- CD73 deficiency does not aggravate angiotensin II-induced aortic inflammation in mice.Scientific reports · 2023Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- The immunomodulatory function of adenosine in sepsis.Frontiers in immunology · 2022Review
- Extracellular cAMP-Adenosine Pathway Signaling: A Potential Therapeutic Target in Chronic Inflammatory Airway Diseases.Frontiers in immunology · 2022Review
- Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward.Journal for immunotherapy of cancer · 2021Review
- Adenosine and Inflammation: Here, There and Everywhere.International journal of molecular sciences · 2021Review
- Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy.International journal of molecular sciences · 2019Review
- Adenosine from a biologic source regulates neutrophil extracellular traps (NETs).Journal of leukocyte biology · 2019Article
- Design and in Vivo Characterization of AJournal of medicinal chemistry · 2019Article
- Activation of adenosine ANeuropharmacology · 2018Article
- Purinergic Regulation of Neutrophil Function.Frontiers in immunology · 2018Review
- The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis.Frontiers in immunology · 2018Review
- Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.Purinergic signalling · 2017Review
- Adenosine effectively restores endotoxin-induced inhibition of human neutrophil chemotaxis via A1 receptor-p38 pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- The Many Faces of the A2b Adenosine Receptor in Cardiovascular and Metabolic Diseases.Journal of cellular physiology · 2015Review
- Characterization of Dahl salt-sensitive rats with genetic disruption of the A2B adenosine receptor gene: implications for A2B adenosine receptor signaling during hypertension.Purinergic signalling · 2015Article
- Selectivity is species-dependent: Characterization of standard agonists and antagonists at human, rat, and mouse adenosine receptors.Purinergic signalling · 2015Article
- Differential Tissue-Specific Function of Adora2b in Cardioprotection.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The formation of adenosine dampens inflammation by inhibiting most cells of the immune system. Among its actions on neutrophils, adenosine suppresses superoxide generation and regulates chemotactic activity. To date, most evidence implicates the G(s) protein-coupled A(2A) adenosine receptor (AR) as the primary AR subtype responsible for mediating the actions of adenosine on neutrophils by stimulating cAMP production. Given that the A(2B)AR is now known to be expressed in neutrophils and that it is a G(s) protein-coupled receptor, we examined in this study whether it signals to suppress neutrophil activities by using 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY 60-6583), a new agonist for the human A(2B)AR that was confirmed in preliminary studies to be a potent and highly selective agonist for the murine A(2B)AR. We found that treating mouse neutrophils with low concentrations (10(-9) and 10(-8) M) of BAY 60-6583 inhibited formylated-methionine-leucine-phenylalanine (fMLP)-stimulated superoxide production by either naive neutrophils, tumor necrosis factor-α-primed neutrophils, or neutrophils isolated from mice treated systemically with lipopolysaccharide. This inhibitory action of BAY 60-6583 was confirmed to involve the A(2B)AR in experiments using neutrophils obtained from A(2B)AR gene knockout mice. It is noteworthy that BAY 60-6583 increased fMLP-stimulated superoxide production at higher concentrations (>1 μM), which was attributed to an AR-independent effect. In a standard Boyden chamber migration assay, BAY 60-6583 alone did not stimulate neutrophil chemotaxis or influence chemotaxis in response to fMLP. These results indicate that the A(2B)AR signals to suppress oxidase activity by murine neutrophils, supporting the idea that this low-affinity receptor for adenosine participates along with the A(2A)AR in regulating the proinflammatory actions of neutrophils.
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Registered trials
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