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A1 and A2A Receptors Modulate Spontaneous Adenosine but Not Mechanically Stimulated Adenosine in the Caudate

Cite this: ACS Chem. Neurosci. 2020, 11, 20, 3377–3385
Publication Date (Web):September 25, 2020
https://doi.org/10.1021/acschemneuro.0c00510
Copyright © 2020 American Chemical Society

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    Abstract

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    Adenosine is a neuromodulator, and rapid increases in adenosine in the brain occur spontaneously or after mechanical stimulation. However, the regulation of rapid adenosine by adenosine receptors is unclear, and understanding it would allow better manipulation of neuromodulation. The two main adenosine receptors in the brain are A1 receptors, which are inhibitory, and A2A receptors, which are excitatory. Here, we investigated the regulation of spontaneous adenosine and mechanically stimulated adenosine by adenosine receptors, using global A1 or A2A knockout mice. Results were compared in vivo and in brain slices’ models. A1 KO mice have increased frequency of spontaneous adenosine events, but no change in the average concentration of an event, while A2A KO mice had no change in frequency but increased average event concentration. Thus, both A1 and A2A self-regulate spontaneous adenosine release; however, A1 acts on the frequency of events, while A2A receptors regulate concentration. The trends are similar both in vivo and slices, so brain slices are a good model system to study spontaneous adenosine release. For mechanically stimulated adenosine, there was no effect of A1 or A2A KO in vivo, but in brain slices, there was a significant increase in concentration evoked in A1KO mice. Mechanically stimulated release was largely unregulated by A1 and A2A receptors, likely because of a different release mechanism than spontaneous adenosine. Thus, A1 receptors affect the frequency of spontaneous adenosine transients, and A2A receptors affect the concentration. Therefore, future studies could probe drug treatments targeting A1 and A2A receptors to increase rapid adenosine neuromodulation.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acschemneuro.0c00510.

    • Distribution of spontaneous adenosine concentration and duration, mechanically stimulated adenosine release is relatively stable for each stimulation, position of the electrode in brain (PDF)

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    Cited By

    This article is cited by 7 publications.

    1. Kailash Shrestha, B. Jill Venton. Transient Adenosine Modulates Serotonin Release Indirectly in the Dorsal Raphe Nuclei. ACS Chemical Neuroscience 2024, 15 (4) , 798-807. https://doi.org/10.1021/acschemneuro.3c00687
    2. Yuanyu Chang, B. Jill Venton. Dual-Channel Electrochemical Measurements Reveal Rapid Adenosine is Localized in Brain Slices. ACS Chemical Neuroscience 2022, 13 (4) , 477-485. https://doi.org/10.1021/acschemneuro.1c00679
    3. Jason R. Borgus, Ying Wang, Dana J. DiScenza, B. Jill Venton. Spontaneous Adenosine and Dopamine Cotransmission in the Caudate-Putamen Is Regulated by Adenosine Receptors. ACS Chemical Neuroscience 2021, 12 (23) , 4371-4379. https://doi.org/10.1021/acschemneuro.1c00175
    4. Lu Wang, Ying-Jie Li, Xu Yang, Bo Yang, Xin Zhang, Jing Zhang, Qi Zhang, Xu-Dong Cheng, Jian-Hong Wang, Neng-Wei Yu. Purinergic signaling: a potential therapeutic target for ischemic stroke. Purinergic Signalling 2023, 19 (1) , 173-183. https://doi.org/10.1007/s11302-022-09905-y
    5. Priyanshi Sikka, Tapan Behl, Parteek Chandel, Aayush Sehgal, Sukhbir Singh, Hafiz A. Makeen, Mohammed Albratty, Hassan A. Alhazmi, Abdulkarim M. Meraya. Scrutinizing the Therapeutic Promise of Purinergic Receptors Targeting Depression. Neurotoxicity Research 2022, 40 (5) , 1570-1585. https://doi.org/10.1007/s12640-022-00550-2
    6. Scott T. Lee, Yuanyu Chang, B. Jill Venton. Pannexin1 channels regulate mechanically stimulated but not spontaneous adenosine release. Analytical and Bioanalytical Chemistry 2022, 414 (13) , 3781-3789. https://doi.org/10.1007/s00216-022-04047-x
    7. Stéphane Marinesco. Micro- and nano-electrodes for neurotransmitter monitoring. Current Opinion in Electrochemistry 2021, 29 , 100746. https://doi.org/10.1016/j.coelec.2021.100746

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