ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Ecto-5'-nucleotidase (CD73)-mediated formation of adenosine is critical for the striatal adenosine A2A receptor functions.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 150 citations in OpenAlex.
- Dual CD73/AFrontiers in pharmacology · 2026Article
- Extracellular Vesicles and Purinergic Signaling in Alzheimer's Disease-Joining Forces for Novel Therapeutic Approach.Brain sciences · 2025Review
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- Mitochondrial Localization and Function of Adenosine Receptors.International journal of biological sciences · 2025Article
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- Impact of Coffee Intake on Measures of Wellbeing in Mice.Nutrients · 2024Article
- Control of Dopamine Signal in High-Order Receptor Complex on Striatal Astrocytes.International journal of molecular sciences · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Effect of Xanthohumol, a Bioactive Natural Compound from Hops, on Adenosine Pathway in Rat C6 Glioma and Human SH-SY5Y Neuroblastoma Cell Lines.Nutrients · 2024Article
- Feedback facilitation by adenosine APurinergic signalling · 2024Article
- 40 Hz light flickering promotes sleep through cortical adenosine signaling.Cell research · 2024Article
- Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission.Current issues in molecular biology · 2023Article
- Purinergic Tuning of the Tripartite Neuromuscular Synapse.Molecular neurobiology · 2023Review
- Adenosine ABiomolecules · 2023Article
- Striatopallidal adenosine ANeuropharmacology · 2023Review
- Increased ATP Release and Higher Impact of Adenosine AMolecular neurobiology · 2023Article
- The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks.Frontiers in cellular neuroscience · 2023Review
- CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine AInternational journal of molecular sciences · 2022Article
- Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?International journal of molecular sciences · 2022Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 5 countries.
Funding
Abstract
Adenosine is a neuromodulator acting through inhibitory A1 receptors (A1Rs) and facilitatory A2ARs, which have similar affinities for adenosine. It has been shown that the activity of intracellular adenosine kinase preferentially controls the activation of A1Rs, but the source of the adenosine activating A2ARs is unknown. We now show that ecto-5'-nucleotidase (CD73), the major enzyme able to convert extracellular AMP into adenosine, colocalizes with A2ARs in the basal ganglia. In addition to astrocytes, striatal CD73 is prominently localized to postsynaptic sites. Notably, CD73 coimmunoprecipitated with A2ARs and proximity ligation assays confirmed the close proximity of CD73 and A2ARs in the striatum. Accordingly, the cAMP formation in synaptosomes as well as the hypolocomotion induced by a novel A2AR prodrug that requires CD73 metabolization to activate A2ARs were observed in wild-type mice, but not in CD73 knock-out (KO) mice or A2AR KO mice. Moreover, CD73 KO mice displayed increased working memory performance and a blunted amphetamine-induced sensitization, mimicking the phenotype of global or forebrain-A2AR KO mice, as well as upon pharmacological A2AR blockade. These results show that CD73-mediated formation of extracellular adenosine is responsible for the activation of striatal A2AR function. This study points to CD73 as a new target that can fine-tune A2AR activity, and a novel therapeutic target to manipulate A2AR-mediated control of striatal function and neurodegeneration.
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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.