Affinage

ADORA2B

Adenosine receptor A2b · UniProt P29275

Length
332 aa
Mass
36.3 kDa
Annotated
2026-04-28
38 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADORA2B is a low-affinity G protein-coupled adenosine receptor that functions as a master tissue-protective signal transducer during hypoxia, ischemia, and inflammation across multiple organ systems. Upon activation by extracellular adenosine—whose availability is regulated by ENT transporters and CD73—ADORA2B signals through cAMP/PKA and MAPK/CREB pathways to stabilize the circadian protein PER2 (which supports HIF-1α-dependent glycolytic metabolism in cardiomyocytes and hippocampal neurons), suppress neutrophil and macrophage TNF-α and IL-6 release, enhance regulatory T cell differentiation, activate SERCA2α-dependent calcium homeostasis, and regulate red blood cell glycolytic flux and antioxidant defenses (PMID:22504483, PMID:22531331, PMID:22389701, PMID:26136425, PMID:41751389, PMID:40905089). ADORA2B expression is transcriptionally induced by HIF-1α during hypoxia and its protein stability is maintained through physical interaction with APIP, which prevents lysosomal degradation; the D296G variant that disrupts APIP binding abolishes cardioprotective activity (PMID:28701304, PMID:31263105). Cell-type-specific functions are prominent: myeloid ADORA2B constrains neutrophil-dependent inflammation in cardiac and renal ischemia-reperfusion injury but drives alternatively activated macrophage-dependent pulmonary fibrosis and hypertension through IL-6 and hyaluronan production, while on pulmonary artery smooth muscle cells it induces vascular remodeling mediators including HAS2 and TGM2 (PMID:23028059, PMID:25318478, PMID:29910735, PMID:27320922).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Establishing the genomic identity of human ADORA2B—chromosomal location (17p12) and gene structure with a coding-region intron—provided the foundational map for all subsequent molecular studies.

    Evidence FISH mapping and genomic cloning with partial sequencing

    PMID:7558011

    Open questions at the time
    • Full promoter characterization not performed
    • No functional data from expression of cloned gene
  2. 2012 High

    Demonstration that ADORA2B stabilizes PER2 during myocardial ischemia, enabling a HIF-1α-dependent metabolic switch to oxygen-efficient glycolysis, revealed the first mechanistic link between adenosine signaling, circadian clock components, and ischemic cardioprotection.

    Evidence Adora2b−/− and Per2−/− mouse ischemic preconditioning models with metabolic profiling and glycolytic enzyme induction

    PMID:22504483

    Open questions at the time
    • Direct biochemical mechanism of PER2 stabilization by ADORA2B not defined
    • Whether PER2 stabilization is cAMP-dependent or uses another second messenger
  3. 2012 High

    Reciprocal bone marrow transplants and neutrophil reconstitution experiments established that ADORA2B on myeloid cells—specifically PMNs—is the critical cell-type locus for suppressing TNF-α-dependent tissue injury in both cardiac and renal ischemia-reperfusion.

    Evidence WT↔Adora2b−/− bone marrow chimeras, neutrophil depletion/reconstitution with Tnf-α−/− neutrophils, myocardial and renal I/R models

    PMID:22531331 PMID:23028059

    Open questions at the time
    • Intracellular signaling cascade from ADORA2B to TNF-α suppression in PMNs not delineated
    • Whether other myeloid subtypes beyond PMNs contribute
  4. 2012 Medium

    Showing that ADORA2B is required for adenosine-driven regulatory T cell differentiation extended its immunomodulatory role beyond innate immunity to adaptive immune tolerance.

    Evidence Adora2b−/− T cells in endotoxin-induced pulmonary inflammation with flow cytometric Treg quantification

    PMID:22389701

    Open questions at the time
    • Whether ADORA2B acts cell-autonomously in T cells versus via antigen-presenting cells not fully resolved
    • Downstream transcription factor linking ADORA2B to FOXP3 induction unknown
  5. 2013 High

    Tissue-specific conditional knockouts revealed that ADORA2B operates through distinct cell-type circuits—alveolar epithelium in acute lung injury, vascular endothelium in diabetic nephropathy—establishing that its protective function is context- and compartment-specific.

    Evidence Alveolar-epithelial and endothelial-specific Adora2b conditional KO mice in ventilator-induced ALI and streptozotocin diabetic nephropathy models

    PMID:23603835 PMID:24262796

    Open questions at the time
    • Whether epithelial versus endothelial ADORA2B engage the same second messenger cascades
    • Downstream targets in endothelial cells not identified
  6. 2013 High

    Identification of ADORA2B as a downstream effector of Fra-1 that promotes filopodia formation and invasive activity in breast cancer introduced a pro-tumorigenic dimension to ADORA2B biology.

    Evidence RNAi, pharmacologic antagonism, and in vivo xenograft lung metastasis assays

    PMID:23483055

    Open questions at the time
    • Whether ADORA2B drives invasion through cAMP or an alternative G-protein pathway not established
    • Relevance to other cancer types unclear
  7. 2014 High

    Myeloid-specific ADORA2B deletion showed that on alternatively activated macrophages ADORA2B drives—rather than suppresses—pathological fibrosis and pulmonary hypertension via IL-6 and hyaluronan, revealing that ADORA2B's role switches from protective to pathogenic depending on chronicity and cell type.

    Evidence Adora2bf/f-LysMCre conditional KO mice in bleomycin lung fibrosis model with IL-6, CD206, arginase-1 readouts

    PMID:25318478

    Open questions at the time
    • Signal that switches ADORA2B from anti-inflammatory to pro-fibrotic not identified
    • Whether receptor desensitization differs between acute and chronic contexts
  8. 2015 High

    Using three independent tissue-specific conditional knockouts in a single study definitively parsed ADORA2B's cardioprotective functions: endothelial and myocyte ADORA2B mediates preconditioning, while myeloid ADORA2B mediates post-ischemic protection.

    Evidence Lyz2-Cre, VE-cadherin-Cre, myosin-Cre × floxed Adora2b mice in myocardial I/R and ischemic preconditioning

    PMID:26136425

    Open questions at the time
    • Distinct downstream effectors in each cell type not characterized
    • Whether preconditioning and reperfusion signals converge on PER2 unknown
  9. 2017 Medium

    Establishing that HIF-1α transcriptionally induces ADORA2B on macrophages created a feedforward HIF-1α→ADORA2B→IL-6 circuit, explaining how hypoxia amplifies macrophage-driven fibrosis.

    Evidence HIF-1α inhibition in bleomycin model plus macrophage differentiation assays and human IPF samples

    PMID:28701304

    Open questions at the time
    • Whether HIF-1α directly binds ADORA2B promoter HREs not shown by ChIP
    • Single lab finding
  10. 2018 High

    PASMC-specific ADORA2B deletion protected from pulmonary hypertension and identified HAS2 and TGM2 as downstream effectors, extending ADORA2B's pathogenic fibrotic axis to smooth muscle cells beyond myeloid cells.

    Evidence Adora2bf/f-Taglncre conditional KO in SUGEN/hypoxia and bleomycin PH models with RVSP and vascular remodeling

    PMID:29910735

    Open questions at the time
    • Whether cAMP or another pathway activates HAS2/TGM2 transcription not defined
    • Interaction with myeloid ADORA2B pathway unknown
  11. 2019 High

    Discovery that APIP physically interacts with ADORA2B and prevents its lysosomal degradation—and that the D296G variant disrupts this interaction and abolishes cardioprotection—provided the first post-translational regulatory mechanism for ADORA2B protein stability.

    Evidence Co-IP, proximity ligation assay, APIP transgenic/heterozygous KO mice, D296G knock-in mice, hypoxia assays

    PMID:31263105

    Open questions at the time
    • Structural basis of APIP–ADORA2B interaction not resolved
    • Whether APIP modulates ADORA2B signaling kinetics beyond stability unknown
  12. 2021 High

    Identification of neutrophil-derived netrin-1 as an endogenous ligand-like activator of myeloid ADORA2B during myocardial I/R revealed an autocrine/paracrine loop that amplifies ADORA2B-dependent cardioprotection.

    Evidence Conditional netrin-1 deletion in neutrophils, recombinant netrin-1 rescue, myocardial I/R, patient samples

    PMID:33891683

    Open questions at the time
    • Whether netrin-1 binds ADORA2B directly or acts through a co-receptor not determined
    • Relative contribution of netrin-1 versus adenosine to ADORA2B activation in vivo unclear
  13. 2023 High

    Genetic epistasis showed that myocyte ENT1 removes extracellular adenosine that otherwise activates myeloid ADORA2B, defining a complete intercellular signaling axis (myocyte ENT1 → adenosine pool → myeloid ADORA2B) controlling cardiac ischemic injury.

    Evidence Myocyte-specific ENT1 KO crossed with myeloid-specific Adora2b KO, cardiac adenosine measurements, I/R model

    PMID:37288658

    Open questions at the time
    • Whether ENT2 has a compensatory role in myocytes not tested
    • Quantitative threshold of extracellular adenosine needed for ADORA2B activation unknown
  14. 2023 Medium

    CD73-derived adenosine signals through ADORA2B to mediate immunosuppression in pancreatic cancer, positioning the CD73-ADORA2B axis as a targetable immune checkpoint in the tumor microenvironment.

    Evidence Genetically engineered and syngeneic PDAC mouse models with CD73 inhibitors, HPLC adenosine measurement, transcriptomics

    PMID:36720042

    Open questions at the time
    • Direct genetic ADORA2B deletion in tumor or immune compartment not performed
    • Which immune cell type mediates ADORA2B-dependent immunosuppression in PDAC not identified
  15. 2025 High

    Demonstration that ADORA2B regulates red blood cell glycolytic flux and antioxidant defenses—and that caffeine impairs this signaling—extended ADORA2B's metabolic regulatory role to erythrocyte biology and transfusion medicine.

    Evidence Adora2b−/− mice storage/transfusion studies, recombinant G6PD inhibition assay, metabolomics in 13,091 human donors

    PMID:40905089

    Open questions at the time
    • Whether ADORA2B acts via cAMP in mature enucleated RBCs not fully confirmed
    • Direct protein interaction between ADORA2B signaling and G6PD not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the APIP–ADORA2B interaction, the molecular switch that converts ADORA2B from tissue-protective to pro-fibrotic in chronic settings, and whether netrin-1 directly binds ADORA2B or requires a co-receptor.
  • No crystal or cryo-EM structure of ADORA2B or ADORA2B–APIP complex
  • Mechanism of cell-type and context-dependent signaling polarity not defined
  • Netrin-1 binding mode to ADORA2B unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 7 GO:0098772 molecular function regulator activity 5
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 1
Partners
APIPHIF1ANT5ENTN1PER2SLC29A1SLC29A2

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Adora2b signaling during myocardial ischemia leads to stabilization of the circadian rhythm protein Per2, which in turn stabilizes HIF-1α, enabling a HIF-dependent metabolic switch to oxygen-efficient glycolysis that is cardioprotective; Per2-/- mice lack this metabolic shift and have larger infarct sizes. Genetic knockout mice (Adora2b-/-, Per2-/-), metabolic studies, ischemic preconditioning model, light-induced Per2 stabilization with transcriptional induction of glycolytic enzymes Nature medicine High 22504483
2012 Adora2b signaling on bone marrow-derived cells, specifically polymorphonuclear neutrophils (PMNs), dampens myocardial ischemia-reperfusion injury by suppressing TNF-α release from PMNs. Bone marrow transplantation between WT and Adora2b-/- mice, neutrophil depletion, Adora2b agonist treatment, cytokine profiling, pharmacologic studies on human activated PMNs Anesthesiology High 22531331
2012 Adora2b signaling on T cells enhances regulatory T cell (Treg) differentiation; Adora2b-/- T cells fail to differentiate into Tregs upon adenosine receptor activation, and Adora2b-deficient mice exhibit more severe endotoxin-induced pulmonary inflammation with impaired Treg induction. Pharmacologic Adora2b activation, Adora2b-/- mice, endotoxin-induced pulmonary inflammation model, flow cytometry for T cell subsets PloS one Medium 22389701
2012 Adora2b signaling on neutrophils constrains TNF-α production during renal ischemia-reperfusion; reconstitution of Adora2b-/- mice with TNF-α-deficient neutrophils rescued the injury phenotype, placing Adora2b upstream of neutrophil-dependent TNF-α in acute kidney injury. Adora2b-/- mice, TNF-α antibody blockade, Tnf-α-/- mice, neutrophil depletion and reconstitution, renal ischemia-reperfusion model Journal of immunology High 23028059
2013 Alveolar epithelial Adora2b signaling mediates ENT2-dependent lung protection during acute lung injury; dipyridamole-dependent attenuation of lung inflammation was abolished in mice with alveolar epithelial Adora2b deletion, establishing a crosstalk pathway between ENT2 and Adora2b. Ent1-/-, Ent2-/- gene-targeted mice, tissue-specific Adora2b deletion in alveolar epithelium, dipyridamole treatment, mechanical ventilation-induced ALI model FASEB journal High 23603835
2013 ADORA2B signaling in breast cancer cells downstream of Fra-1 transcription factor promotes filopodia formation and invasive activity; RNAi silencing or pharmacologic blockade of ADORA2B inhibited filopodia formation, invasion in vitro, and tumor outgrowth in lungs in vivo. Stable RNAi depletion, pharmacologic ADORA2B antagonism, in vivo xenograft metastasis assays, synthetic lethal drug screen Proceedings of the National Academy of Sciences of the United States of America High 23483055
2013 ADORA2B signaling on vascular endothelium mediates protection from diabetic nephropathy; tissue-specific deletion of Adora2b in vascular endothelia (but not tubular epithelia) worsened nephropathy, and selective Adora2b agonist treatment was protective. Tissue-specific conditional knockout mice (endothelial vs. tubular), streptozotocin diabetic model, transgenic Adora2b reporter mice, selective agonist (BAY 60-6583) treatment Journal of the American Society of Nephrology : JASN High 24262796
2013 ADORA2B acts as a mechanoreceptor in enterochromaffin (EC) cells; under hypoxia, ADORA2B activates HIF-1α signaling via MAPK/CREB pathways and phosphorylates TPH-1 and activates VMAT-1 to stimulate serotonin (5-HT) synthesis and secretion. Hypoxia experiments on EC cells and IBD mucosa, antisense knockdown, NECA agonist, MRS1754 antagonist, Renilla luciferase under HRE control, PCR/western blot PloS one Medium 23638125
2014 ADORA2B signaling on myeloid cells (alternatively activated macrophages) drives lung fibrosis and pulmonary hypertension; conditional deletion of ADORA2B on myeloid cells attenuated fibrosis and PH with reduced IL-6, hyaluronan, CD206, and arginase-1. Conditional knockout mice (Adora2Bf/f-LysMCre), bleomycin-induced lung injury model, bronchoalveolar lavage, histology, lung function measurements FASEB journal High 25318478
2015 ADORA2B mediates different cardioprotective mechanisms in a tissue-specific manner: endothelial and myocyte Adora2b mediates ischemic preconditioning, while inflammatory cell (PMN) Adora2b is required for protection from ischemia-reperfusion injury; adoptive transfer of Adora2b-/- PMNs confirmed the PMN-specific role. Tissue-specific conditional knockout mice (Lyz2-Cre, VE-cadherin-Cre, myosin-Cre crossed to floxed Adora2b), myocardial I/R and IP models, cytokine profiling, adoptive PMN transfer Journal of immunology High 26136425
1995 The human ADORA2B gene is located on chromosome 17p12; its pseudogene maps to chromosome 1q32. Partial sequence revealed an intron interrupting the coding region at the second intracellular loop, similar to A1 and A2a adenosine receptor genes. Fluorescence in situ hybridization (FISH), genomic cloning, partial sequence analysis Genomics High 7558011
2016 Sevoflurane's hepatoprotective effects during liver ischemia-reperfusion require Adora2b signaling; sevoflurane inhibited platelet-neutrophil complex formation and reduced liver damage in wild-type but not Adora2b-/- mice, and increased Adora2b transcription and expression in liver tissue. Adora2b-/- and Adora2a-/- mice, liver IR model, flow cytometry, immunohistochemistry, real-time PCR, ex vivo human blood experiments Anesthesiology Medium 27404219
2016 Sustained activation of adenosine A2B receptors on myeloid cells promotes chronic pain by inducing nociceptor hyperexcitability via soluble IL-6 receptor trans-signaling; this mechanism was demonstrated in ADA-deficient mice, sickle cell disease mice, and CFA inflammatory pain models. Ada-/- mice, sickle cell disease mouse model, CFA inflammatory pain model, myeloid-specific ADORA2B manipulation, behavioral pain assays Cell reports High 27320922
2017 HIF1A transcriptionally upregulates ADORA2B expression on alternatively activated macrophages; HIF1A inhibition reduces ADORA2B expression on AAMs and disrupts AAM differentiation and IL-6 production, establishing HIF1A→ADORA2B as a regulatory axis in pulmonary fibrosis. HIF1A inhibitor in bleomycin mouse model, ADORA2B deletion/pharmacological antagonism, cultured macrophage differentiation assays, human IPF lung samples FASEB journal Medium 28701304
2018 ADORA2B signaling in pulmonary artery smooth muscle cells (PASMCs) mediates development of pulmonary hypertension through induction of IL-6, hyaluronan synthase 2 (HAS2), and tissue transglutaminase (Tgm2); ADORA2Bf/f-Taglncre mice were protected from PH development. ADORA2Bf/f-Taglncre conditional knockout mice, SUGEN/hypoxia and bleomycin PH models, RVSP measurement, Fulton index, vascular remodeling histology, RT-PCR in PASMCs Frontiers in physiology High 29910735
2019 APIP (Apaf-1-interacting protein) physically interacts with ADORA2B, stabilizing both proteins by interfering with lysosomal degradation, and activates downstream PKA-CREB signaling; knockdown of APIP impairs ADORA2B cytoprotective effects; the ADORA2B D296G variant (rs200741295) fails to bind APIP and loses cardioprotective activity. Co-immunoprecipitation, proximity ligation assay, APIP transgenic mice, Apip+/- mice, ADORA2B D296G knock-in mice, hypoxia cell death assays, AKT-HIF1α pathway analysis Cell death & disease High 31263105
2020 Hippocampal ADORA2B regulates Per2 expression and cognitive function; Adora2b-/- mice show reduced hippocampal PER2 protein and impaired T-maze alternation; ADORA2B agonist BAY-60-6583 restored midazolam-induced cognitive dysfunction and hippocampal Per2 levels; C-fos was downregulated in Adora2b-/- hippocampus. Adora2b-/- mice, midazolam treatment, BAY-60-6583 agonist administration, T-maze behavioral assay, hippocampal mRNA/protein expression analysis Current pharmaceutical design Medium 32294028
2021 Neutrophil-derived netrin-1 is elevated during myocardial ischemia-reperfusion and attenuates cardiac injury through myeloid adenosine A2b receptor (ADORA2B) signaling, establishing an autocrine signaling loop between neutrophil netrin-1 and myeloid ADORA2B. Conditional netrin-1 deletion in neutrophils (Ntn1loxP/loxP Lyz2Cre+), neutrophil depletion, recombinant netrin-1 treatment, pharmacologic studies in myocardial I/R model, patient blood samples The Journal of experimental medicine High 33891683
2021 CXCR4 and CXCR7 inhibition reduces platelet-neutrophil complex and NET formation through Adora2b signaling; protective effects of CXCR4/CXCR7 antagonism were abolished in Adora2b-/- mice, placing ADORA2B downstream of CXCR4/CXCR7 in inflammatory cell activation. Adora2b-/- mice, zymosan- and fecal-induced sepsis models, flow cytometry, histology, in vitro human platelet/PMN assays International journal of molecular sciences Medium 34948374
2023 Myocyte-specific ENT1 limits cardioprotection by removing extracellular adenosine; ENT1 deletion in myocytes (Ent1loxP/loxP Myosin Cre+) reduced infarct sizes; cardioprotection from ENT inhibition required myeloid Adora2b signaling (abolished in Adora2bloxP/loxP LysM Cre+ mice), revealing a myocyte ENT1→extracellular adenosine→myeloid Adora2b axis. Tissue-specific conditional knockout mice (myocyte ENT1, myeloid Adora2b), dipyridamole treatment, cardiac adenosine level measurements, myocardial I/R model JCI insight High 37288658
2023 CD73-dependent extracellular adenosine signals through Adora2b to mediate immunosuppression in pancreatic ductal adenocarcinoma; CD73 small-molecule inhibitors reduced tumor development, and Adora2b was identified as a determinant of adenosine-mediated immunosuppression. Genetically engineered and syngeneic mouse PDAC models, CD73 small-molecule inhibitors, multiplex immunofluorescence, HPLC adenosine measurement, transcriptomic analysis Cancer research Medium 36720042
2021 Long-term cigarette smoke extract exposure upregulates CD73 and ADORA2B expression, increases adenosine production, inhibits PKC alpha activity and p-ERK signaling, and impairs airway wound repair; knockdown of ADORA2B activates PKC alpha and restores p-ERK signaling, placing ADORA2B upstream of PKC alpha/ERK in chronic airway injury. Long-term CSE exposure cell model, ADORA2B and CD73 knockdown, PKC alpha and p-ERK assays, in vivo double knockout CD73/ADORA2B mice, wound closure assays Frontiers in physiology Medium 33584346
2024 ADORA2B promotes ferroptosis in chondrocytes by inhibiting the PI3K/Akt pathway; MYC acts as a transcriptional suppressor of ADORA2B (confirmed by dual-luciferase reporter and ChIP assays), and overexpression of ADORA2B reverses MYC-mediated protection from ferroptosis. ADORA2B knockdown/overexpression in chondrocytes, dual-luciferase reporter gene assay, ChIP assay, PI3K/Akt inhibitor (LY294002), MYC overexpression, in vivo OA mouse model Environmental toxicology Medium 38174997
2025 Caffeine inhibits ADORA2B signaling in red blood cells, impairing glycolytic flux and antioxidant defenses; Adora2b-deficient mice showed impaired glycolytic flux, compromised antioxidant defenses, and decreased transfusion efficacy; caffeine also directly inhibits recombinantly expressed G6PD. Adora2b-/- mouse model, murine storage/transfusion studies, recombinant G6PD inhibition assay, human donor cohort (13,091 donors), metabolomics Haematologica High 40905089
2023 Dexmedetomidine alleviates pulmonary fibrosis by downregulating ADORA2B expression and suppressing ADORA2B-mediated MAPK pathway activation, thereby inhibiting myofibroblast differentiation; ADORA2B agonist (BAY60-6583) reversed the anti-fibrotic effects of dexmedetomidine. Bleomycin mouse model, TGF-β-induced myofibroblast model in vitro, MAPK pathway assays, BAY60-6583 agonist pharmacologic rescue Respiratory research Medium 37644529
2026 ADORA2B activates the cAMP/PKA/PLB/SERCA2α signaling axis in cardiomyocytes; LA treatment activates ADORA2B leading to PKA-mediated phosphorylation of phospholamban, enhanced SERCA2α activity, and prevention of calcium overload; ADORA2B antagonist (MRS1754) partially reversed these effects. H9C2 cardiomyocyte H/R model, network pharmacology, ADORA2B antagonist (MRS1754), PKA/PLB/SERCA2α protein phosphorylation and expression assays, LDH/cTnI release assays Current issues in molecular biology Medium 41751389

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia. Nature medicine 271 22504483
2013 Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis. Proceedings of the National Academy of Sciences of the United States of America 145 23483055
2013 Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 93 23603835
2012 Adora2b adenosine receptor engagement enhances regulatory T cell abundance during endotoxin-induced pulmonary inflammation. PloS one 90 22389701
2014 Deletion of ADORA2B from myeloid cells dampens lung fibrosis and pulmonary hypertension. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 67 25318478
2017 HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 63 28701304
2016 Sustained Elevated Adenosine via ADORA2B Promotes Chronic Pain through Neuro-immune Interaction. Cell reports 58 27320922
2012 Adora2b signaling on bone marrow derived cells dampens myocardial ischemia-reperfusion injury. Anesthesiology 42 22531331
2013 CD73-dependent generation of adenosine and endothelial Adora2b signaling attenuate diabetic nephropathy. Journal of the American Society of Nephrology : JASN 41 24262796
2021 PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling. The Journal of experimental medicine 39 33891683
2012 Adora2b adenosine receptor signaling protects during acute kidney injury via inhibition of neutrophil-dependent TNF-α release. Journal of immunology (Baltimore, Md. : 1950) 39 23028059
2023 CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer. Cancer research 35 36720042
1995 Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene. Genomics 35 7558011
2015 Differential Tissue-Specific Function of Adora2b in Cardioprotection. Journal of immunology (Baltimore, Md. : 1950) 34 26136425
2018 Switching-Off Adora2b in Vascular Smooth Muscle Cells Halts the Development of Pulmonary Hypertension. Frontiers in physiology 23 29910735
2013 The stimulatory adenosine receptor ADORA2B regulates serotonin (5-HT) synthesis and release in oxygen-depleted EC cells in inflammatory bowel disease. PloS one 21 23638125
2023 The resurgence of the Adora2b receptor as an immunotherapeutic target in pancreatic cancer. Frontiers in immunology 20 37187740
2016 Adenosine Receptor Adora2b Plays a Mechanistic Role in the Protective Effect of the Volatile Anesthetic Sevoflurane during Liver Ischemia/Reperfusion. Anesthesiology 20 27404219
2021 CXCR4 and CXCR7 Inhibition Ameliorates the Formation of Platelet-Neutrophil Complexes and Neutrophil Extracellular Traps through Adora2b Signaling. International journal of molecular sciences 19 34948374
2015 The association of ADORA2A and ADORA2B polymorphisms with the risk and severity of chronic heart failure: a case-control study of a northern Chinese population. International journal of molecular sciences 19 25629231
2022 Alternative adenosine Receptor activation: The netrin-Adora2b link. Frontiers in pharmacology 17 35910389
2023 Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling. JCI insight 16 37288658
2019 Cardioprotective role of APIP in myocardial infarction through ADORA2B. Cell death & disease 14 31263105
2016 ADORA2b Signaling in Cardioprotection. Journal of nature and science 12 27747290
2024 ADORA2B, transcriptionally suppressing by MYC, promotes ferroptosis of chondrocytes via inhibition of the PI3K/Akt pathway in mice with osteoarthritis. Environmental toxicology 8 38174997
2023 Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway. Respiratory research 8 37644529
2021 Co-inhibition of CD73 and ADORA2B Improves Long-Term Cigarette Smoke Induced Lung Injury. Frontiers in physiology 7 33584346
2020 Adenosine receptor Adora2b antagonism attenuates Brucella abortus 544 infection in professional phagocyte RAW 264.7 cells and BALB/c mice. Veterinary microbiology 6 32122590
2020 A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction. Current pharmaceutical design 6 32294028
2023 Salvianolic acid B attenuates diabetic nephropathy through alleviating ADORA2B, NALP3 in flammasome, and NFκB activity. Canadian journal of physiology and pharmacology 5 38070193
2020 Does ischemic preconditioning increase flap survival by ADORA2B receptor activation? Clinical hemorheology and microcirculation 5 31985456
2025 Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity. Haematologica 3 40905089
2007 The promoter regions of the Myb-regulated Adora2B and Mcm4 genes co-localize with origins of DNA replication. BMC molecular biology 2 17822556
2025 Ghrelin suppresses apoptosis and autophagy in osteoarthritis synovial cells by modulating the ADORA2B/PI3K/Akt/mTOR signaling pathway. Journal of orthopaedics 1 39995546
2025 To verify the biological characteristics of disulfidptosis associated gene ADORA2B in esophageal cancer. BMC gastroenterology 1 40389870
2026 Levistolide A Alleviates Myocardial Ischemia-Reperfusion Injury Partly by Improving Calcium Homeostasis via the ADORA2B/cAMP/PKA/PLB/SERCA2α Signaling Axis. Current issues in molecular biology 0 41751389
2025 Caffeine Impairs Red Blood Cell Storage Quality by Dual Inhibition of ADORA2b Signaling and G6PD Activity. bioRxiv : the preprint server for biology 0 40502093
2025 Potential of Adora2b as an immunotherapeutic target for gastric cancer. Frontiers in immunology 0 41346607