ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 98 citations in OpenAlex.
- Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.JCI insight · 2025Trial
- Ghrelin suppresses apoptosis and autophagy in osteoarthritis synovial cells by modulating the ADORA2B/PI3K/Akt/mTOR signaling pathway.Journal of orthopaedics · 2025Article
- Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.Nature communications · 2024Article
- Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.The Journal of physiology · 2024Review
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- Adenosine 2A Receptor Agonism Improves Survival in Extracorporeal Cardiopulmonary Resuscitation.The Journal of surgical research · 2024Article
- Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.Cell reports. Medicine · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Hypoxia-adenosine axis as therapeutic targets for acute respiratory distress syndrome.Frontiers in immunology · 2024Review
- Addressing the Clinical Importance of Equilibrative Nucleoside Transporters in Drug Discovery and Development.Clinical pharmacology and therapeutics · 2023Review
- In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.Purinergic signalling · 2023Article
- Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.JCI insight · 2023Article
- IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.EMBO reports · 2023Article
- A Pharmacodynamic Evaluation of the Protective Effects of Roxadustat Against Hypoxic Injury at High Altitude.Drug design, development and therapy · 2023Article
- Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.PLoS pathogens · 2022Article
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- An overview of current therapeutic strategies for glioblastoma and the role of CD73 as an alternative curative approach.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1.Cells · 2022Article
- Bim Expression Promotes the Clearance of Mononuclear Phagocytes during Choroidal Neovascularization, Mitigating Scar Formation in Mice.Life (Basel, Switzerland) · 2022Article
- Update on the recent development of allosteric modulators for adenosine receptors and their therapeutic applications.Frontiers in pharmacology · 2022Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The signaling molecule adenosine has been implicated in attenuating acute lung injury (ALI). Adenosine signaling is terminated by its uptake through equilibrative nucleoside transporters (ENTs). We hypothesized that ENT-dependent adenosine uptake could be targeted to enhance adenosine-mediated lung protection. To address this hypothesis, we exposed mice to high-pressure mechanical ventilation to induce ALI. Initial studies demonstrated time-dependent repression of ENT1 and ENT2 transcript and protein levels during ALI. To examine the contention that ENT repression represents an endogenous adaptive response, we performed functional studies with the ENT inhibitor dipyridamole. Dipyridamole treatment (1 mg/kg; EC50=10 μM) was associated with significant increases in ALI survival time (277 vs. 395 min; P<0.05). Subsequent studies in gene-targeted mice for Ent1 or Ent2 revealed a selective phenotype in Ent2(-/-) mice, including attenuated pulmonary edema and improved gas exchange during ALI in conjunction with elevated adenosine levels in the bronchoalveolar fluid. Furthermore, studies in genetic models for adenosine receptors implicated the A2B adenosine receptor (Adora2b) in mediating ENT-dependent lung protection. Notably, dipyridamole-dependent attenuation of lung inflammation was abolished in mice with alveolar epithelial Adora2b gene deletion. Our newly identified crosstalk pathway between ENT2 and alveolar epithelial Adora2b in lung protection during ALI opens possibilities for combined therapies targeted to this protein set.
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