ArticleThe Journal of pharmacology and experimental therapeutics2016
Peripheral Adenosine A3 Receptor Activation Causes Regulated Hypothermia in Mice That Is Dependent on Central Histamine H1 Receptors.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Using thermal preference to understand mouse thermal biology.American journal of physiology. Endocrinology and metabolism · 2026Article
- NExperimental neurology · 2024Article
- In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.Purinergic signalling · 2023Article
- Article
- Perineuronal nets affect memory and learning after synapse withdrawal.Translational psychiatry · 2022Article
- Truncated (N)-Methanocarba Nucleosides as Partial Agonists at Mouse and Human AJournal of medicinal chemistry · 2020Article
- Activation of neuronal adenosine A1 receptors causes hypothermia through central and peripheral mechanisms.PloS one · 2020Article
- Physiology and effects of nucleosides in mice lacking all four adenosine receptors.PLoS biology · 2019Article
- Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development.Frontiers in cellular neuroscience · 2019Review
- Activation of adenosine ANeuropharmacology · 2018Article
- Melanotan II causes hypothermia in mice by activation of mast cells and stimulation of histamine 1 receptors.American journal of physiology. Endocrinology and metabolism · 2018Article
- A binding kinetics study of human adenosine ABiochemical pharmacology · 2018Article
- Pharmacophore-based tailoring of biphenyl amide derivatives as selective 5-hydroxytryptamine 2B receptor antagonists.MedChemComm · 2018Article
- Pyruvate induces torpor in obese mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Bitopic fluorescent antagonists of the AMedChemComm · 2017Article
- Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters.Journal of medicinal chemistry · 2017Article
- Hypothermia in mouse is caused by adenosine ANeuropharmacology · 2017Article
- Article
- Purinergic Signaling in Mast Cell Degranulation and Asthma.Frontiers in pharmacology · 2017Review
- Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HTJournal of medicinal chemistry · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Adenosine can induce hypothermia, as previously demonstrated for adenosine A1 receptor (A1AR) agonists. Here we use the potent, specific A3AR agonists MRS5698, MRS5841, and MRS5980 to show that adenosine also induces hypothermia via the A3AR. The hypothermic effect of A3AR agonists is independent of A1AR activation, as the effect was fully intact in mice lacking A1AR but abolished in mice lacking A3AR. A3AR agonist-induced hypothermia was attenuated by mast cell granule depletion, demonstrating that the A3AR hypothermia is mediated, at least in part, via mast cells. Central agonist dosing had no clear hypothermic effect, whereas peripheral dosing of a non-brain-penetrant agonist caused hypothermia, suggesting that peripheral A3AR-expressing cells drive the hypothermia. Mast cells release histamine, and blocking central histamine H1 (but not H2 or H4) receptors prevented the hypothermia. The hypothermia was preceded by hypometabolism and mice with hypothermia preferred a cooler environmental temperature, demonstrating that the hypothermic state is a coordinated physiologic response with a reduced body temperature set point. Importantly, hypothermia is not required for the analgesic effects of A3AR agonists, which occur with lower agonist doses. These results support a mechanistic model for hypothermia in which A3AR agonists act on peripheral mast cells, causing histamine release, which stimulates central histamine H1 receptors to induce hypothermia. This mechanism suggests that A3AR agonists will probably not be useful for clinical induction of hypothermia.
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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.