Role of striatal A2A receptor subpopulations in neurological disorders

Sergi Ferré, César Quiroz, Marco Orrú, Xavier Guitart, Seema Gulyani, Richard Allen, Christopher J. Earley

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationAdenosine
Subtitle of host publicationA Key Link between Metabolism and Brain Activity
PublisherSpringer New York
Pages179-197
Number of pages19
Volume9781461439035
ISBN (Electronic)9781461439035
ISBN (Print)1461439027, 9781461439028
DOIs
StatePublished - Nov 1 2013

Keywords

  • Adenosine A receptor
  • Huntington disease
  • Parkinson's disease
  • Receptor heteromers
  • Restless Legs Syndrome
  • Striatum

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

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    Ferré, S., Quiroz, C., Orrú, M., Guitart, X., Gulyani, S., Allen, R., & Earley, C. J. (2013). Role of striatal A2A receptor subpopulations in neurological disorders. In Adenosine: A Key Link between Metabolism and Brain Activity (Vol. 9781461439035, pp. 179-197). Springer New York. https://doi.org/10.1007/978-1-4614-3903-5_9