Adenosine is a homeostatic modulator in all cells, being produced from intracellular ATP as a consequence of increased workload or noxious stimuli. Extracellular adenosine can then afford tissue protection by a combination of effects operated by inhibitory A1 receptors, which refrain metabolism, and facilitatory A2A receptors, which cause vasodilatation and act as a potent “Off” signal of immune/inflammatory cells in the periphery. Adenosine also acts as a neuromodulator in the brain through A1 receptor-mediated inhibition of excitatory transmission. However, adenosine also aggravates brain damage in chronic neurodegenerative conditions by mechanisms that may involve an A2A receptor-mediated potentiation of neuroinflammation. We will now review the evidences suggesting that A2A receptor control neuroinflammation and discuss the possible mechanisms underlying the opposite modulation by A2A receptors of peripheral inflammation and neuroinflammation.
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Cunha, R.A., Chen, JF., Sitkovsky, M.V. (2007). Opposite Modulation of Peripheral Inflammation and Neuroinflammation by Adenosine A2A Receptors. In: Malva, J.O., Rego, A.C., Cunha, R.A., Oliveira, C.R. (eds) Interaction Between Neurons and Glia in Aging and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-70830-0_3
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