Affinage

ADORA2A

Adenosine receptor A2a · UniProt P29274

Length
412 aa
Mass
44.7 kDa
Annotated
2026-04-28
73 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADORA2A is a Gs-coupled adenosine receptor that constitutively activates adenylyl cyclase to elevate intracellular cAMP upon adenosine binding, serving as a major signaling hub linking purinergic tone to neural, vascular, metabolic, and proliferative programs (PMID:2125216). In the brain, ADORA2A is selectively expressed on enkephalinergic D2-type medium spiny neurons of the striatum and forms functional heterodimers with dopamine receptor DRD2 that modulate ERK signaling in retinal and striatal circuits (PMID:1713612, PMID:35724635, PMID:41533917). Beyond cAMP/PKA, ADORA2A engages ERK/MYC, STAT3/AKT, and PI3K/AKT cascades to drive context-dependent outcomes including neuroendocrine lineage reprogramming through proline metabolism-driven H3K27 deacetylation, blood–brain barrier tight-junction maintenance in endothelial cells, placental angiogenesis, white adipose lipolysis via epigenetic de-repression of hormone-sensitive lipase, and vascular smooth muscle ferroptosis (PMID:38099497, PMID:30886019, PMID:37051927, PMID:39976204, PMID:40401372). ADORA2A also suppresses macrophage apoptosis by inhibiting caspase-3 cleavage downstream of JMJD3-mediated H3K27me3 demethylation (PMID:36456564).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1990 High

    Establishing ADORA2A as a functional adenosine A2 receptor answered the question of whether the orphan gene RDC8 encoded a ligand-gated GPCR capable of constitutive adenylyl cyclase activation.

    Evidence Heterologous expression in COS7, Y1, thyrocyte, and oocyte systems with radioligand binding and adenylyl cyclase assays

    PMID:2125216

    Open questions at the time
    • No structural data on receptor–Gs coupling
    • Endogenous signaling partners not yet identified
    • Constitutive vs. ligand-gated activity ratio in native tissue unknown
  2. 1991 High

    Resolving which neuronal populations express ADORA2A showed it is restricted to enkephalinergic (D2-type) medium spiny neurons in the striatum, establishing the cellular context for its neuromodulatory role.

    Evidence In situ hybridization with neuronal subtype markers in rat brain

    PMID:1713612

    Open questions at the time
    • Expression in non-striatal brain regions or non-neuronal cells not surveyed
    • Functional consequence of cell-type restriction not tested
  3. 1996 High

    Mapping the human ADORA2A gene to chromosome 22q11.2 and defining its two-exon structure provided the genomic framework for subsequent genetic association studies.

    Evidence Genomic cloning, FISH, and human-hamster hybrid cell panel PCR

    PMID:8670304

    Open questions at the time
    • Regulatory elements and promoter architecture not characterized
    • No disease-associated variants identified at this locus
  4. 2013 Medium

    Demonstrating that a common ADORA2A haplotype modulates receptor expression and cAMP output linked human genetic variation to quantitative differences in adenosine signaling.

    Evidence SNP genotyping with mRNA, protein, and cAMP assays in lymphoblasts

    PMID:23535492

    Open questions at the time
    • Causal variant within the haplotype not resolved
    • Relevance to brain-expressed ADORA2A not directly tested
  5. 2019 High

    Endothelial-specific Adora2a deletion revealed that ADORA2A is the receptor mediating insulin resistance-associated blood–brain barrier breakdown, tight junction degradation, and consequent hippocampal dysfunction.

    Evidence Inducible endothelial CKO mice with BBB permeability, electron microscopy, LTP, and behavioral assays; replicated by pharmacological antagonism

    PMID:30886019

    Open questions at the time
    • Direct molecular target linking ADORA2A to tight junction protein turnover unidentified
    • Whether other adenosine receptors compensate long-term not tested
  6. 2020 Medium

    Identification of miR-497/miR-195 as direct negative regulators of ADORA2A, silenced by promoter methylation, established an epigenetic–post-transcriptional axis controlling cAMP/PKA-driven osteogenic differentiation.

    Evidence Luciferase reporter validation, demethylation with 5-aza-dC, miRNA overexpression/knockdown, cAMP/PKA readout

    PMID:32432317

    Open questions at the time
    • In vivo significance of miR-497/195-ADORA2A axis in ossification not confirmed
    • Whether this regulatory axis operates in other cell types unknown
  7. 2022 Medium

    Demonstrating ADORA2A–DRD2 heterodimer formation in retinal epithelial cells and showing that JMJD3-mediated H3K27me3 demethylation transcriptionally upregulates ADORA2A in macrophages expanded the receptor's known interaction partners and upstream epigenetic control mechanisms.

    Evidence Co-IP and immunofluorescence for ADORA2A-DRD2 in RPE cells; ChIP and siRNA in LPS-treated macrophages and ALI mouse model

    PMID:35724635 PMID:36456564

    Open questions at the time
    • Stoichiometry and structural basis of ADORA2A-DRD2 heterodimer unresolved
    • Whether JMJD3-mediated regulation is tissue-specific not determined
  8. 2023 High

    ADORA2A was shown to rewire proline metabolism through ERK/MYC/PYCR, promoting SIRT6/7-dependent H3K27 deacetylation that drives neuroendocrine lineage plasticity; separately, ADORA2A signaling through STAT3/AKT was established as a placental pro-angiogenic pathway and a renal cytoprotective mechanism.

    Evidence Adora2a KO GEMMs with ChIP, metabolomics, and epistasis (neuroendocrine); in vivo Matrigel/IUGR models with pSTAT3/pAKT (placenta); renal IR injury model with bidirectional ADORA2A manipulation (kidney)

    PMID:36932924 PMID:37051927 PMID:38099497

    Open questions at the time
    • How proline sensing by SIRT6/7 is mechanistically coupled remains unclear
    • Whether STAT3/AKT and ERK/MYC branches are activated simultaneously or context-selectively is unknown
  9. 2024 High

    Retina-specific Adora2a knockout and Drd2-CKO epistasis demonstrated that ADORA2A promotes myopia through a required ADORA2A–DRD2 interaction in the retina, while brain-specific RagA overexpression placed ADORA2A downstream of mTOR signaling in depressive behavior.

    Evidence Retinal CKO and pharmacological antagonism with Drd2-CKO epistasis; RagA transgenic mice with RNA-seq, proteomics, and behavioral rescue by istradefylline

    PMID:39373701 PMID:41533917

    Open questions at the time
    • Intracellular signaling cascade linking ADORA2A-DRD2 to myopia-related scleral remodeling not defined
    • Mechanism by which RagA/p70S6K elevates ADORA2A expression is not determined
  10. 2025 Medium

    Two studies extended ADORA2A's metabolic roles: one showed ADORA2A/Rap1 mediates PARP1-POLG–triggered VSMC ferroptosis and vascular calcification, and another demonstrated that CD73-derived adenosine activates ADORA2A to reduce HSL promoter methylation and drive adipose lipolysis.

    Evidence VSMC-specific Parp1 CKO with AAV9 POLG knockdown and Adora2a inhibition; Adora2a KO mice with rescue, DNA methylation, and metabolic phenotyping on HFD

    PMID:39976204 PMID:40401372

    Open questions at the time
    • How ADORA2A signaling targets DNA methyltransferases at the HSL promoter is unresolved
    • Whether Rap1 is the sole downstream mediator of ADORA2A-dependent ferroptosis is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of ADORA2A–DRD2 heterodimer formation, the tissue-specific logic selecting among divergent downstream cascades (cAMP/PKA, ERK/MYC, STAT3/AKT, PI3K/AKT, Rap1), and the mechanisms by which ADORA2A signaling modifies the epigenome at specific loci remain to be determined.
  • No atomic-resolution structure of ADORA2A-DRD2 heterodimer
  • No unified model for context-dependent pathway selection
  • Epigenetic targeting specificity (which loci, which writers/erasers) is poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-4839726 Chromatin organization 2
Partners
DRD2JMJD3MYCPYCR1RAP1ASIRT6SIRT7STAT3
Complex memberships
ADORA2A-DRD2 heterodimer

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 RDC8 (ADORA2A) encodes an adenosine A2 receptor that constitutively activates adenylyl cyclase and the cAMP cascade; expression in COS7 cells conferred adenosine A2 binding characteristics, and this constitutive activity was inhibited by adenosine deaminase and adenosine A2 receptor antagonists. Heterologous expression in Y1 adrenal cells, dog thyrocytes, Xenopus oocytes, and COS7 cells; radioligand binding assay; adenylyl cyclase activity assay Biochemical and biophysical research communications High 2125216
1991 ADORA2A (RDC8) is selectively expressed by enkephalinergic medium spiny neurons in the striatum (caudate-putamen), but not by substance P-containing or cholinergic neurons. In situ hybridization histochemistry combined with neuronal subtype markers in rat brain Journal of neurochemistry High 1713612
1996 The human ADORA2A gene is organized into two exons interrupted by an ~6.4 kb intron and is chromosomally localized to 22q11.2 by fluorescent in situ hybridization and PCR analysis of hybrid cell panels. Genomic cloning, sequence analysis, FISH, PCR of human-hamster hybrid cell panels Biochemical and biophysical research communications High 8670304
2013 The ADORA2A AA diplotype (haplotype A of rs2298383/rs5751876/rs35320474/rs4822492) is associated with higher ADORA2A mRNA and protein expression and increased cAMP production in lymphoblasts in response to adenosine, linking a genetic variant to altered intracellular adenosine/cAMP signaling. SNP genotyping, mRNA expression (qPCR), protein expression (Western blot), cAMP production assay in lymphoblasts Neurology Medium 23535492
2019 Endothelial cell-specific deletion of Adora2a protects mice from diet-induced insulin resistance-associated blood-brain barrier (BBB) breakdown, demonstrating that Adora2a signaling in vascular endothelial cells mediates tight junction erosion, vascular inflammation, and consequent deficits in hippocampal synaptic plasticity and cognition. Inducible endothelial-specific Adora2a knockout mice; BBB permeability assays (sodium fluorescein, Evans blue); transmission electron microscopy of tight junctions; acute pharmacological antagonism; hippocampal LTP recording; behavioral memory tasks The Journal of neuroscience High 30886019
2023 ADORA2A activation rewires proline metabolism through an ERK/MYC/PYCR cascade; increased proline synthesis promotes SIRT6/7-mediated deacetylation of H3K27, biasing transcription toward a neuroendocrine lineage profile. Genetic ablation of Adora2a in mouse models inhibits neuroendocrine prostate and lung cancer development. Genetically engineered mouse models (Adora2a KO); pharmacological ADORA2A blockade in vivo; transcriptomic and metabolic analyses; ChIP for H3K27ac; epistasis with ERK/MYC/PYCR pathway inhibitors The Journal of clinical investigation High 38099497
2022 JMJD3-mediated H3K27me3 demethylation upregulates ADORA2A expression, which in turn inhibits caspase-3 cleavage to suppress macrophage apoptosis in LPS-induced acute lung injury; C/EBPβ also enhances ADORA2A expression downstream of H3K27me3 demethylation. Chromatin immunoprecipitation; LPS-induced ALI mouse model and RAW264.7 cell model; TUNEL staining; flow cytometry apoptosis assay; Western blot; siRNA knockdown of JMJD3 and ADORA2A Cell death discovery Medium 36456564
2023 Adenosine activates ADORA2A to promote phosphorylation of STAT3 and AKT, resulting in increased angiogenin (Ang)-dependent angiogenesis in placenta; ADORA2A expression is downregulated in IUGR placenta and adenosine supplementation improves IUGR outcomes in mice. In vitro angiogenesis assays; in vivo Matrigel plug assays; Western blot for pSTAT3 and pAKT; diet-induced IUGR mouse model; ADORA2A expression quantification Arteriosclerosis, thrombosis, and vascular biology Medium 37051927
2023 ADORA2A promotes colorectal carcinoma cell proliferation and inhibits apoptosis via the PI3K/AKT signaling pathway, modulating Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9 levels. siRNA knockdown and plasmid overexpression of ADORA2A in CRC cell lines; CCK-8, colony formation, wound healing, transwell assays; flow cytometry apoptosis; Western blot for PI3K/AKT and apoptosis proteins Scientific reports Medium 37945707
2020 miR-497 and miR-195 directly target ADORA2A; promoter CpG island methylation silences the miR-497-195 cluster, leading to upregulation of ADORA2A which activates the cAMP/PKA signaling pathway and promotes osteogenic differentiation of posterior longitudinal ligament cells. Luciferase reporter assay (miRNA target validation); methylation analysis with demethylation reagent 5-aza-2'-deoxycytidine; overexpression and knockdown of miR-195/miR-497; cAMP/PKA pathway readout by Western blot; osteogenic factor expression The Biochemical journal Medium 32432317
2025 PARP1-mediated PARylation of POLG triggers its ubiquitination and downregulation, causing mitochondrial dysfunction and activating Adora2a/Rap1 signaling to induce VSMC ferroptosis and vascular calcification; Adora2a inhibition attenuates this process. VSMC knockout mouse models (Parp1flox/flox Tagln Cre+); AAV9-mediated POLG knockdown; RNA-sequencing; Western blot for PARylation and Adora2a/Rap1; functional calcification and ferroptosis assays Arteriosclerosis, thrombosis, and vascular biology Medium 40401372
2025 AMP is converted to adenosine by ecto-5'-nucleotidase (CD73), and adenosine activates ADORA2A signaling to reduce DNA methylation at the hormone-sensitive lipase (HSL) promoter, thereby promoting HSL transcription and white adipose tissue lipolysis; ADORA2A knockout abolishes these metabolic benefits. ADORA2A knockout mice; ADORA2A re-expression rescue; DNA methylation analysis; HSL transcription assay; metabolic phenotyping in high-fat diet mice Advanced science Medium 39976204
2022 ADORA2A and DRD2 form heterodimers in human retinal pigment epithelial (RPE) cells, as demonstrated by immunofluorescence colocalization and co-immunoprecipitation; the adenosine receptor antagonist 7-methylxanthine inhibits ADORA2A expression and increases DRD2 and downstream pERK1/2 signaling. Immunofluorescence; co-immunoprecipitation; siRNA knockdown of DRD2; Western blot for ERK1/2 and pERK1/2; CCK-8 and flow cytometry for cell viability Ophthalmic research Medium 35724635
2024 Caffeine pretreatment reduces hippocampal Il1b expression and downregulates Adora2a expression in mice; LPS reverses caffeine-induced Adora2a downregulation. Bioinformatics identified MAPK3, ARRB2, and ADORA2B as network connectors to ADORA2A's extended signaling network. In vivo mouse model (caffeine + LPS); qPCR for Adora2a and cytokines; DNA methyltransferase expression analysis; bioinformatics network analysis Brain research Low 38494098
2024 Brain-specific RagA overexpression elevates ADORA2A expression and phospho-p70S6K in the prefrontal cortex; pharmacological inhibition of ADORA2A with istradefylline attenuates depressive-like behaviors in RagA transgenic mice, placing ADORA2A downstream of RagA/p70S6K in a depression-related signaling pathway. RagA transgenic mice; RNA-seq of prefrontal cortex; Western blot for ADORA2A and p70S6K; behavioral testing with ADORA2A antagonist; metabolomics and proteomics Advanced science Medium 39373701
2024 Retina-specific AdoRA2a knockout (AdoRA2a-CKO) mice show attenuated form deprivation myopia progression; AdoRA2a and Drd2 are colocalized in the retina, and the selective AdoRA2a antagonist KW6002 fails to inhibit myopia in Drd2-CKO mice, demonstrating that retinal AdoRA2a promotes myopia progression through an AdoRA2a-Drd2 interaction mechanism. Retina-specific CKO mice; pharmacological AdoRA2a antagonism (KW6002); Drd2-CKO epistasis experiment; immunolocalization of AdoRA2a and Drd2; refractive error measurement Investigative ophthalmology & visual science High 41533917
2024 A MiniPromoter derived from ADORA2A regulatory regions (Ple389) drives selective gene expression in D2-receptor-positive medium spiny neurons in the striatum of mice and non-human primates when delivered via rAAV, validated by co-localization with dopamine D2 receptor and DARPP32 markers. rAAV-PHP.B delivery in mice (IV and ICV) and non-human primates (ICV); immunohistochemistry for D2R and DARPP32 co-localization; comparison of 12 MiniPromoter designs Scientific reports Medium 39548191
2023 Genistein activates ADORA2A and thereby inhibits oxidative stress and apoptosis in renal cells; ADORA2A overexpression mimics genistein's protective effect against hypoxia/reoxygenation injury, while ADORA2A knockdown attenuates genistein-induced protection. In vivo renal IR injury mouse model; NRK-52E cell H/R model; ADORA2A overexpression and knockdown (KO cells); oxidative stress and apoptosis assays Human & experimental toxicology Medium 36932924

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. Journal of neurochemistry 465 1713612
1990 RDC8 codes for an adenosine A2 receptor with physiological constitutive activity. Biochemical and biophysical research communications 259 2125216
2007 A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clinical pharmacology and therapeutics 180 17329997
2010 Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 140 20520601
2011 Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. European journal of neurology 87 21281405
2019 Endothelial Adora2a Activation Promotes Blood-Brain Barrier Breakdown and Cognitive Impairment in Mice with Diet-Induced Insulin Resistance. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 30886019
2012 Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation. British journal of pharmacology 74 21950736
2017 Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease. Neurobiology of aging 61 28941407
2013 ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus. Neurology 61 23535492
2009 Adenosine A(2A) receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder. European child & adolescent psychiatry 58 19565319
2009 A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease. Neurobiology of disease 57 19591938
2011 ADORA2A Gene variation, caffeine, and emotional processing: a multi-level interaction on startle reflex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 45 22012471
2020 Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players. Genes 42 32823594
2019 The Impact of Genetic Variations in ADORA2A in the Association between Caffeine Consumption and Sleep. Genes 40 31817803
2018 Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study. Purinergic signalling 39 30511252
2016 Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2. Neuroepidemiology 37 28135712
2010 Age at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1. Neurogenetics 37 20512606
1996 Characterization and chromosomal localization of the human A2a adenosine receptor gene: ADORA2A. Biochemical and biophysical research communications 32 8670304
2023 ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers. The Journal of clinical investigation 29 38099497
2012 Effects of ADORA2A gene variation and caffeine on prepulse inhibition: a multi-level risk model of anxiety. Progress in neuro-psychopharmacology & biological psychiatry 28 22940476
2016 Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX-treated pediatric patients affected by hematological malignancies. Pediatric blood & cancer 27 27399166
2015 Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients? Pharmacogenomics 26 25872644
2019 Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD. Progress in neuro-psychopharmacology & biological psychiatry 25 30946941
2019 Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine's Effect on Postprandial Glycaemia. Scientific reports 25 31324842
2021 ADORA2A-AS1 Restricts Hepatocellular Carcinoma Progression via Binding HuR and Repressing FSCN1/AKT Axis. Frontiers in oncology 22 34733789
2020 ADORA2A variation and adenosine A1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation. Translational psychiatry 19 33235193
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
2020 Coffee effectively attenuates impaired attention in ADORA2A C/C-allele carriers during chronic sleep restriction. Progress in neuro-psychopharmacology & biological psychiatry 18 33373678
2012 Differential effects of ADORA2A gene variations in pre-attentive visual sensory memory subprocesses. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 17 22240468
2016 Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy. Neurochemical research 16 27038930
2016 ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 16 27262510
2023 Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway. Arteriosclerosis, thrombosis, and vascular biology 15 37051927
2020 Genetic Polymorphism of ADORA2A Is Associated With the Risk of Epilepsy and Predisposition to Neurologic Comorbidity in Chinese Southern Children. Frontiers in neuroscience 15 33262686
2015 Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 14 26066465
2020 Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats. Journal of ethnopharmacology 13 32473369
2019 Association between ADORA2A gene polymorphisms and schizophrenia in the North Chinese Han population. Neuropsychiatric disease and treatment 13 31695381
2023 ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma. Scientific reports 12 37945707
2022 H3K27 tri-demethylase JMJD3 inhibits macrophage apoptosis by promoting ADORA2A in lipopolysaccharide-induced acute lung injury. Cell death discovery 12 36456564
2016 The association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypes. Sleep medicine 12 28215251
2020 Serum expression of EAAT2 and ADORA2A in patients with different degrees of Alzheimer's disease. European review for medical and pharmacological sciences 11 33275249
2022 Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer's Disease. International journal of molecular sciences 10 36430879
2025 PARylation of POLG Mediated by PARP1 Accelerates Ferroptosis-Induced Vascular Calcification via Activating Adora2a/Rap1 Signaling. Arteriosclerosis, thrombosis, and vascular biology 9 40401372
2024 Adora2A downregulation promotes caffeine neuroprotective effect against LPS-induced neuroinflammation in the hippocampus. Brain research 8 38494098
2022 Knockdown of ADORA2A antisense RNA 1 inhibits cell proliferation and enhances imatinib sensitivity in chronic myeloid leukemia. Bioengineered 8 35034552
2024 Brain Specific RagA Overexpression Triggers Depressive-Like Behaviors in Mice via Activating ADORA2A Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39373701
2023 The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake. Nutrients 7 37049474
2020 The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity. International journal of molecular sciences 7 32182774
2024 Effect of ADORA2A Gene Polymorphism and Acute Caffeine Supplementation on Hormonal Response to Resistance Exercise: A Double-Blind, Crossover, Placebo-Controlled Study. Nutrients 6 38931158
2023 Synergistic Anti-Tumor Effect of Toosendanin and Paclitaxel on Triple-Negative Breast Cancer via Regulating ADORA2A-EMT Related Signaling. Advanced biology 6 37401656
2021 Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms. Life (Basel, Switzerland) 6 34685481
2020 Analysis of association of ADORA2A and ADORA3 polymorphisms genotypes/haplotypes with efficacy and toxicity of methotrexate in patients with Rheumatoid arthritis. The pharmacogenomics journal 6 32448869
2020 The impact of single nucleotide polymorphisms in ADORA2A and ADORA3 genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study. International journal of rheumatic diseases 6 32969158
2017 The plausible association of MTHFR and ADORA2A polymorphisms with nodules in rheumatoid arthritis patients treated with methotrexate. Pharmacogenetics and genomics 6 27846189
2025 Adenosine Monophosphate Improves Lipolysis in Obese Mice by Reducing DNA Methylation via ADORA2A Activation by Ecto-5'-Nucleotidase (CD73). Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39976204
2020 Methylation-mediated down-regulation of microRNA-497-195 cluster confers osteogenic differentiation in ossification of the posterior longitudinal ligament of the spine via ADORA2A. The Biochemical journal 5 32432317
2023 Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A. Genes 4 36833216
2023 Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy. Frontiers in pharmacology 4 37063258
2019 ADORA2A Polymorphisms Influence Methotrexate Adverse Events in Rheumatoid Arthritis. The Israel Medical Association journal : IMAJ 4 31140226
2024 Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection. International journal of molecular sciences 3 38892324
2024 New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates. Scientific reports 3 39548191
2023 Genistein attenuates renal ischemia-reperfusion injury via ADORA2A pathway. Human & experimental toxicology 3 36932924
2023 Peripheral Expression of ADORA2A Is Increased and Is Correlated with Autism Spectrum Disorder Severity in a Sample of Turkish Children. Psychiatry and clinical psychopharmacology 3 38764528
2022 7-Methylxanthine Influences the Behavior of ADORA2A-DRD2 Heterodimers in Human Retinal Pigment Epithelial Cells. Ophthalmic research 3 35724635
2018 Adenosine A2A receptor gene polymorphisms (ADORA2A) are associated with maximal concentric contraction pain. Meta gene 3 37560748
2025 Caffeine exacerbates exercise-induced gut cell damage and is influenced by ADORA2A genotype but not CYP1A2 genotype: A preliminary study. Physiological reports 1 41261949
2024 Epigenetics and suicide: investigating altered H3K14ac unveiled differential expression in ADORA2A, B4GALT2 and MMP14. Epigenomics 1 38545853
2024 Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer. International journal of molecular sciences 1 38731962
2022 The Influence of ADORA2A on Levodopa-Induced Dyskinesia. Neurology India 1 35532631
2022 Can the Brazilian Caffeine Expectancy Questionnaires Differentiate the CYP1A2 and ADORA2A Gene Polymorphisms?-An Exploratory Study with Brazilian Athletes. Nutrients 1 36014860
2020 Impact of the Polymorphism rs5751876 of the Purinergic Receptor ADORA2A on Periprocedural Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention. Journal of atherosclerosis and thrombosis 1 33342966
2026 Inhibition of Retinal AdoRA2a Activity Attenuates Myopia Progression. Investigative ophthalmology & visual science 0 41533917
2025 Association study of ADORA2A gene polymorphisms with adverse drug reactions to valproic acid and oxcarbazepine in the treatment of children with epilepsy. Epilepsia 0 40751907
2025 Precision Targeting in Gastric Cancer: AI-Driven Discovery of MET, ADORA2A, CDK5R1, and ADORA1. Assay and drug development technologies 0 40932634