ArticlePLoS biology2019
Physiology and effects of nucleosides in mice lacking all four adenosine receptors.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Using thermal preference to understand mouse thermal biology.American journal of physiology. Endocrinology and metabolism · 2026Article
- Continuous sampling of cerebrospinal fluid from the third ventricle of the hypothalamus to identify accumulating or depleting metabolites during hibernation.The Journal of experimental biology · 2026Article
- Biphasic actions of the adenosine A2a receptor antagonist istradefylline in mice with obstructive uropathy.Scientific reports · 2025Article
- P2YACS pharmacology & translational science · 2025Article
- A novel combination therapy with Uridine and Praziquantel effectively alleviates schistosomiasis-induced hepatic fibrosis through promoting adipogenic differentiation.PLoS pathogens · 2025Article
- Selective modulation of epileptic tissue by an adenosine ABritish journal of pharmacology · 2024Article
- Unraveling the enigma: housekeeping geneFrontiers in psychiatry · 2024Article
- In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.Purinergic signalling · 2023Article
- Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation.International journal of molecular sciences · 2023Article
- The impact of inosine on hippocampal synaptic transmission and plasticity involves the release of adenosine through equilibrative nucleoside transporters rather than the direct activation of adenosine receptors.Purinergic signalling · 2023Article
- New paradigms in purinergic receptor ligand discovery.Neuropharmacology · 2023Review
- AInternational review of neurobiology · 2023Article
- Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation.Frontiers in pharmacology · 2023Review
- Anti-obesity effects of the dual-active adenosine AInternational journal of obesity (2005) · 2022Article
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells.Cell death discovery · 2022Article
- Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects.The Journal of clinical investigation · 2022Article
- Adenosine ABritish journal of pharmacology · 2022Review
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- AEuropean journal of medicinal chemistry · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Adenosine is a constituent of many molecules of life; increased free extracellular adenosine indicates cell damage or metabolic stress. The importance of adenosine signaling in basal physiology, as opposed to adaptive responses to danger/damage situations, is unclear. We generated mice lacking all four adenosine receptors (ARs), Adora1-/-;Adora2a-/-;Adora2b-/-;Adora3-/- (quad knockout [QKO]), to enable investigation of the AR dependence of physiologic processes, focusing on body temperature. The QKO mice demonstrate that ARs are not required for growth, metabolism, breeding, and body temperature regulation (diurnal variation, response to stress, and torpor). However, the mice showed decreased survival starting at about 15 weeks of age. While adenosine agonists cause profound hypothermia via each AR, adenosine did not cause hypothermia (or bradycardia or hypotension) in QKO mice, indicating that AR-independent signals do not contribute to adenosine-induced hypothermia. The hypothermia elicited by adenosine kinase inhibition (with A134974), inosine, or uridine also required ARs, as each was abolished in the QKO mice. The proposed mechanism for uridine-induced hypothermia is inhibition of adenosine transport by uridine, increasing local extracellular adenosine levels. In contrast, adenosine 5'-monophosphate (AMP)-induced hypothermia was attenuated in QKO mice, demonstrating roles for both AR-dependent and AR-independent mechanisms in this process. The physiology of the QKO mice appears to be the sum of the individual knockout mice, without clear evidence for synergy, indicating that the actions of the four ARs are generally complementary. The phenotype of the QKO mice suggests that, while extracellular adenosine is a signal of stress, damage, and/or danger, it is less important for baseline regulation of body temperature.
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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.