ArticleThe Journal of clinical investigation2016
A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 87 citations in OpenAlex.
- The effect of an adenosine AFluids and barriers of the CNS · 2018Trial
- The effect of regadenoson on the integrity of the human blood-brain barrier, a pilot study.Journal of neuro-oncology · 2017Trial
- The sleep-deprived blood-brain barrier: Does the Brain's gatekeeper adapt or merely fail slowly?Neurobiology of sleep and circadian rhythms · 2026Review
- Adenosine A2A signaling in mood disorders: How far have we come?IBRO neuroscience reports · 2025Article
- Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.Discover oncology · 2025Review
- An Evaluation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Carbamazepine-Resistant Rats.International journal of molecular sciences · 2025Article
- In Situ Mass Spectrometry Imaging to Elucidate the Effects of an Adenosine AACS pharmacology & translational science · 2025Article
- Know Your ABCs: Discovery, Differentiation, and Targeting of T-Bet+ B Cells.Immunological reviews · 2025Review
- The mCell death and differentiation · 2025Article
- Neoantigens in cancer immunoediting: from mechanisms to personalized vaccines in breast cancer.Frontiers in cell and developmental biology · 2025Review
- Adenosine receptor subtype modulators: Insight into molecular mechanisms and their therapeutic application.American journal of translational research · 2025Review
- The Neuroprotective Role of A2A Adenosine Purinoceptor Modulation as a Strategy Against Glioblastoma.Brain sciences · 2024Review
- The Brain-Heart Network of Syncope.International journal of molecular sciences · 2024Review
- Review
- A Neutrophil Hijacking Nanoplatform Reprograming NETosis for Targeted Microglia Polarizing Mediated Ischemic Stroke Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening.Acta pharmaceutica Sinica. B · 2024Article
- Strategies for Drug Delivery into the Brain: A Review on Adenosine Receptors Modulation for Central Nervous System Diseases Therapy.Pharmaceutics · 2023Review
- Review
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The blood-brain barrier (BBB) protects the brain from toxic substances within the peripheral circulation. It maintains brain homeostasis and is a hurdle for drug delivery to the CNS to treat neurodegenerative diseases, including Alzheimer's disease and brain tumors. The drug efflux transporter P-glycoprotein (P-gp) is highly expressed on brain endothelial cells and blocks the entry of most drugs delivered to the brain. Here, we show that activation of the A2A adenosine receptor (AR) with an FDA-approved A2A AR agonist (Lexiscan) rapidly and potently decreased P-gp expression and function in a time-dependent and reversible manner. We demonstrate that downmodulation of P-gp expression and function coincided with chemotherapeutic drug accumulation in brains of WT mice and in primary mouse and human brain endothelial cells, which serve as in vitro BBB models. Lexiscan also potently downregulated the expression of BCRP1, an efflux transporter that is highly expressed in the CNS vasculature and other tissues. Finally, we determined that multiple pathways, including MMP9 cleavage and ubiquitinylation, mediated P-gp downmodulation. Based on these data, we propose that A2A AR activation on BBB endothelial cells offers a therapeutic window that can be fine-tuned for drug delivery to the brain and has potential as a CNS drug-delivery technology.
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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.