ArticleCellular signalling2016
The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 145 citations in OpenAlex.
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- ERK1/2 activation in anti-inflammatory effects and underlying signaling mechanisms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- From Gut Homeostasis to Colorectal Cancer: Spatial and Temporal Reprogramming of Microbial Inosine Signaling.Biomedicines · 2026Review
- AMetabolites · 2026Article
- Intestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation.Journal of biomedical science · 2026Article
- Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective.Frontiers in immunology · 2026Article
- Roseburia intestinalis-derived inosine improves intestinal motility by activating TGF-β1/p-Smad3/Transgelin signaling axis.Journal of translational medicine · 2025Article
- Inosine shapes PD-1 blockade responses and synergizes with dual PD-1/CTLA-4 immunotherapy to enhance antitumor immunity.Cancer immunology, immunotherapy : CII · 2025Article
- Tumour initiated purinergic signalling promotes cardiomyocyte RBFOX1 degradation and cardiotoxicity from DNA damaging anticancer agents.Nature communications · 2025Article
- Norepinephrine signals through astrocytes to modulate synapses.Science (New York, N.Y.) · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- The gut microbiome and cancer: from tumorigenesis to therapy.Nature metabolism · 2025Review
- Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia-induced immunosuppression.JCI insight · 2025Article
- The impact of purine nucleosides on neuroplasticity in the adult brain.Purinergic signalling · 2025Review
- Multifaceted role of inosine in complex diseases and human health.Nutrition reviews · 2025Review
- GLP-1RAs attenuated obesity and reversed leptin resistance partlyActa pharmaceutica Sinica. B · 2025Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell-based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7μM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38μM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo.
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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.