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Extracellular adenosine acts through a class of G protein-coupled receptors (GPCRs), defined across mammalian species as A1, A2A, A2B, and A3ARs (adenosine receptors). Adenosine has a cytoprotective and allostatic role in the body, both in the periphery and in the central nervous system. Following binding of adenosine, or another naturally occurring agonist, the receptor interacts with heterotrimeric G proteins and β-arrestin to stimulate or inhibit downstream signaling cascades, or to induce receptor desensitization.
The purine nucleoside adenosine, as a natural local modulator of cell action, increases the ratio of oxygen supply to demand, suppresses excessive inflammation, and promotes tissue protection against apoptosis or ischemic damage. ARs also have effects on proliferation and differentiation. Nearly every cell type in the body expresses one or more of these receptors, indicating the fundamental...