ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Antagonistic interaction between adenosine A2A receptors and Na+/K+-ATPase-α2 controlling glutamate uptake in astrocytes.
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 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
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- Adenosine A2A receptor signaling in neuroinflammation, glial modulation, and mechanisms associated with chronic pain.Purinergic signalling · 2026Review
- Modulation of hierarchical motor sequence learning by alpha-synuclein and the adenosine ANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Adenosine APurinergic signalling · 2026Article
- Therapeutic Potential Target of Adenosine for Epilepsy: Focusing on Its Interaction with the Molecular Epileptogenic Network.Biomolecules · 2026Review
- The emerging role of astrocytes in spatial cognition, action and Alzheimer's disease.Frontiers in cellular neuroscience · 2026Review
- Aberrant adenosine ANature communications · 2025Article
- Adenosine A2A signaling in mood disorders: How far have we come?IBRO neuroscience reports · 2025Article
- Upregulation of adenosine AMolecular psychiatry · 2025Article
- Adenosine ANeuropharmacology · 2025Article
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- SCH58261 effectively prevents the reduction in excitability of striatal MSNs in mice following 20 h of sleep deprivation.Purinergic signalling · 2025Article
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- 40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.Cell discovery · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Natural brain state change with E/I balance shifting toward inhibition is associated with vigilance impairment.iScience · 2023Article
- Adenosine ABiomolecules · 2023Article
- Pharmacological Characterization of P626, a Novel Dual Adenosine ABiomolecules · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Astrocytic glutamate transporter-1 (GLT-I) is critical to control the bulk of glutamate uptake and, thus, to regulate synaptic plasticity and excitotoxicity. GLT-I glutamate uptake is driven by the sodium gradient implemented by Na(+)/K(+)-ATPases (NKAs) and the α2 subunit of NKA (NKA-α2) is actually linked to GLT-I to regulate astrocytic glutamate transport. We recently found that adenosine A2A receptors (A2ARs), which control synaptic plasticity and neurodegeneration, regulate glutamate uptake through unknown mechanisms. Here we report that A2AR activation decreases NKA activity selectively in astrocytes to inhibit glutamate uptake. Furthermore, we found a physical association of A2ARs with NKA-α2s in astrocytes, as gauged by coimmunoprecipitation and in situ proximity ligation assays, in the cerebral cortex and striatum, two brain regions where A2ARs inhibit the astrocytic glutamate uptake. Moreover, the selective deletion of A2ARs in astrocytes (using Gfa2-A2AR-KO mice) leads to a concurrent increase of both astrocytic glutamate uptake and NKA-α2 levels and activity in the striatum and cortex. This coupling of astrocytic A2ARs to the regulation of glutamate transport through modulation of NKA-α2 activity provides a novel mechanism linking neuronal activity to ion homeostasis controlling glutamatergic activity, all of which are processes intricately associated with the etiology of several brain diseases.
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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.