ArticleProceedings of the National Academy of Sciences of the United States of America2001
Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 1 of them a synthesis that pooled it.
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Who cites it
198 citing papers in PubMed, 1 synthesis or guideline pooled it, 504 citations in OpenAlex.
- Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.Progress in neuro-psychopharmacology & biological psychiatry · 2015Pooled it
- Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Trial
- Enterochromaffin cells as a cellular integration hub for cooperative microbial signaling to modulate gut serotonin and motility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Increased ADORA1 expression in pancreatic islets coincides with insulin secretory defects in human type 2 diabetes.The Journal of biological chemistry · 2026Article
- Adenosine ABiomolecules & therapeutics · 2026Review
- Caffeine: a potential mechanism for anti-obesity.Purinergic signalling · 2025Review
- Development and Preclinical Evaluation of PET Radiotracers Targeting Adenosine AACS medicinal chemistry letters · 2025Article
- Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Adenosine Receptors as Potential Therapeutic Analgesic Targets.International journal of molecular sciences · 2023Review
- The role of the ATP-adenosine axis in ischemic stroke.Seminars in immunopathology · 2023Review
- Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease.Science advances · 2023Article
- The role of adenosine receptor ligands on inflammatory pain: possible modulation of TRPV1 receptor function.Inflammopharmacology · 2023Article
- Small molecule allosteric modulation of the adenosine AFrontiers in endocrinology · 2023Review
- Epilepsy and Autism Spectrum Disorder (ASD): The Underlying Mechanisms and Therapy Targets Related to Adenosine.Current neuropharmacology · 2023Review
- A1 Adenosine Receptor Activation Inhibits P2X3 Receptor-Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons.Molecular neurobiology · 2022Article
- The Role of the Adenosine System on Emotional and Cognitive Disturbances Induced by Ethanol Binge Drinking in the Immature Brain and the Beneficial Effects of Caffeine.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Caffeine and Its Neuroprotective Role in Ischemic Events: A Mechanism Dependent on Adenosine Receptors.Cellular and molecular neurobiology · 2022Review
- Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review.International journal of molecular sciences · 2022Review
- Neurochemical and Behavioral Consequences of Ethanol and/or Caffeine Exposure: Effects in Zebrafish and Rodents.Current neuropharmacology · 2022Review
138 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A(1)R (A(1)R(-/-)). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R. In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A(1)Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important.
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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.