Use of knockout mice to explore CNS effects of adenosine.

Autor: Lopes CR; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal., Lourenço VS; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal., Tomé ÂR; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, Portugal., Cunha RA; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal. Electronic address: cunharod@gmail.com., Canas PM; CNC- Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2021 May; Vol. 187, pp. 114367. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1016/j.bcp.2020.114367
Abstrakt: The initial exploration using pharmacological tools of the role of adenosine receptors in the brain, concluded that adenosine released as such acted on A 1 R to inhibit excitability and glutamate release from principal neurons throughout the brain and that adenosine A 2A receptors (A 2A R) were striatal-'specific' receptors controlling dopamine D 2 R. This indicted A 1 R as potential controllers of neurodegeneration and A 2A R of psychiatric conditions. Global knockout of these two receptors questioned the key role of A 1 R and instead identified extra-striatal A 2A R as robust controllers of neurodegeneration. Furthermore, transgenic lines with altered metabolic sources of adenosine revealed a coupling of ATP-derived adenosine to activate A 2A R and a role of A 1 R as a hurdle to initiate neurodegeneration. Additionally, cell-selective knockout of A 2A R unveiled the different roles of A 2A R in different cell types (neurons/astrocytes) in different portions of the striatal circuits (dorsal versus lateral) and in different brain areas (hippocampus/striatum). Finally, a new transgenic mouse line with deletion of all adenosine receptors seems to indicate a major allostatic rather than homeostatic role of adenosine and may allow isolating P2R-mediated responses to unravel their role in the brain, a goal close to heart of Geoffrey Burnstock, to whom we affectionately dedicate this review.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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