Adenosine A2A-dopamine D2 receptor-receptor heteromers. Targets for neuro-psychiatric disorders

Sergi Ferré, Francisco Ciruela, Meritxell Canals, Daniel Marcellino, Javier Burgueno, Vicent Casadó, Joëlle Hillion, Maria Torvinen, Francesca Fanelli, Piero De Benedetti, Steven R. Goldberg, Michel Bouvier, Kjell Fuxe, Luigi F. Agnati, Carme Lluis, Rafael Franco, Amina Woods

Research output: Contribution to journalArticleResearchpeer-review

124 Citations (Scopus)

Abstract

Emerging evidence shows that G protein-coupled receptors can form homo- and heteromers. These include adenosine A2A receptor-dopamine D 2 receptor heteromers, which are most probably localized in the dendritic spines of the striatopallidal GABAergic neurons, where they are in a position to modulate glutamatergic neurotransmission. The discovery of A 2A receptor-dopamine D2 receptor heteromers gives a frame for the well-known antagonistic interaction between both receptors, which is the bases for a new therapeutic approach for neuro-psychiatric disorders, such as Parkinson's disease and schizoprenia. The present review deals mainly with the biochemical and molecular aspects of A2A receptor-dopamine D 2 receptor interactions. Recent results at the molecular level show that A2A receptor-dopamine D2 receptor heteromers represent the first example of epitope-epitope electrostatic interaction underlying receptor heteromerization. Most probably A2A receptor-D2 receptor heteromerization is not static, but subject to a dynamic regulation, related to the phosphorylation dependence of the A 2A receptor epitope and to the ability of the D2 receptor epitope to bind different partners. Finding out the mechanisms involved in this dynamic regulation can have important implications for the treatment of basal ganglia disorders, schizophrenia and drug addiction.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalParkinsonism & Related Disorders
Volume10
Issue number5
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

Keywords

  • Adenosine A receptor
  • Dopamine D receptor
  • Drug addiction
  • Epitope-epitope interaction
  • Heteromers
  • Parkinson's disease
  • Schizophrenia

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