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Role of Striatal A2A Receptor Subpopulations in Neurological Disorders

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Adenosine

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Abstract

A very significant density of adenosine A2A receptors (A2AR) is present in the striatum, where they are preferentially localized postsynaptically in enkephalinergic-GABAergic-medium spiny neurons (enkephalinergic MSN). In this localization, different subpopulations of A2AR with different functions exist. Their differential function seems to depend mostly on their ability to form heteromers with other G-protein-coupled receptors, such as dopamine D2, cannabinoid CB1 and glutamate mGlu5 receptors. Furthermore, striatal A2AR are also localized presynaptically, in corticostriatal glutamatergic terminals that contact dynorphinergic-GABAergic-medium spiny neurons (dynorphinergic MSN). These presynaptic A2AR heteromerize with A1 receptors and their activation facilitates glutamate release. Pharmacological tools are becoming available that allow the functional evaluation of some of these different subpopulations of A2AR, which can therefore provide selective targets for drug development in different basal ganglia disorders. In fact, alterations in the function of different A2AR subpopulations have recently been observed in Parkinson’s disease and in animal models of Huntington disease and Restless Legs Syndrome.

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Acknowledgments

Work supported by NIDA IRP funds.

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Authors and Affiliations

  1. Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD, 21224, USA

    Sergi Ferré, César Quiroz, Marco Orrú & Xavier Guitart

  2. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Seema Gulyani, Richard Allen & Christopher J. Earley

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  1. Sergi Ferré
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  2. César Quiroz
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  3. Marco Orrú
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  4. Xavier Guitart
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  5. Seema Gulyani
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  6. Richard Allen
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  7. Christopher J. Earley
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Correspondence to Sergi Ferré .

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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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Ferré, S. et al. (2013). Role of Striatal A2A Receptor Subpopulations in Neurological Disorders. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_9

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