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Downstream Pathways of Adenosine

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Adenosine

Abstract

Adenosine belongs to the class of neuromodulators rather than neurotransmitters, since it is not stored in vesicles, nor released by exocytosis as a classical neurotransmitter. Moreover, it does not induce synaptic potentials but influences the release and the action of neurotransmitters. This mostly occurs through interactions with other G protein-coupled receptors as well as of receptors for neurotrophic factors, ion channels, ionotropic receptors, and neurotransmitter transporters. The actions of adenosine are operated by four different G protein-coupled membrane receptors (A1, A2A, A2B, A3), which activate several downstream signaling pathways, the main focus of the present review. Cross talk between adenosine receptors and receptors for neurotransmitters or other neuromodulators may result from interactions between common signaling cascades, as well as through receptor–receptor interactions, including receptor heteromerization. The key receptor in this synaptic interplay appears to be the A2A receptor, whereas A1 receptors mainly act as modulators of neurotransmitter release or by counteracting A2A receptor-mediated actions. We herein review some of the most recent data on the regulation of adenosine availability, as well as on the consequences of adenosine actions in synapses and the corresponding downstream signaling pathways. Moreover, we discuss how activation of adenosine receptors and regulation of extracellular adenosine levels is operated by combined mechanisms. It is highlighted that modulation of neuronal activity by adenosine involves a diversity of enzymes, receptors and signaling cascades that act in a concerted way to fine tune the activity of neurons and glia, including astrocyte-to-neuron signaling.

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Acknowledgments

The work in the authors’ laboratory is supported by research grants from Faculdade de Medicina, Fundação para a Ciência e Tecnologia (FCT), Gulbenkian Foundation, and the European Union (COST B30).

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  1. Faculty of Medicine and Unit of Neurosciences, Institute of Pharmacology and Neurosciences, Institute of Molecular Medicine, University of Lisbon, Av. Professor Egas Moniz, Edifício Egas Moniz, Lisbon, 1649-028, Portugal

    Ana M. Sebastião, Sofia Cristóvão-Ferreira & Joaquim A. Ribeiro

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  1. Ana M. Sebastião
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  2. Sofia Cristóvão-Ferreira
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  3. Joaquim A. Ribeiro
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Correspondence to Ana M. Sebastião .

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Sebastião, A.M., Cristóvão-Ferreira, S., Ribeiro, J.A. (2013). Downstream Pathways of Adenosine. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_7

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