An update on adenosine A2A-dopamine D2 receptor interactions: Implications for the function of G protein-coupled receptors

S. Ferré, C. Quiroz, A. S. Woods, R. Cunha, P. Popoli, F. Ciruela, C. Lluis, R. Franco, K. Azdad, S. N. Schiffmann

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


Adenosine A2A-dopamine D2 receptor interactions play a very important role in striatal function. A2A-D2 receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagonistic interactions between A2A and D2 receptors in the same neurons, the GABAergic enkephalinergic neurons. An antagonistic A2A-D2 intrumembrane receptor interaction, which depends on A2A-D2 receptor heteromerization and Gq/11-PLC signaling, modulates neuronal excitability and neurotransmitter release. On the other hand, an antagonistic A2A-D2 receptor interaction at the adenylyl-cyclase level, which depends an Gg/olf- and Gl/o type V adenylyl-cyclase signaling, modulates protein phosphorylation and gene expression. Finally, under conditions of upregulation of an activator of G protein signaling (AGS3), such as during chronic treatment with addictive drugs, a synergistic A2A-D2 receptor interaction can also be demonstrated. AGS3 facilitates a synergistic interaction between Gg/ olf - and Gi/o-coupled receptors on the activation of types II/IV adenylyl cyclase, leading to a paradoxical increase in protein phosphorylation and gene expression upon co-activation of A2A and D2 receptors. The analysis A2-D2 receptor interactions will have implications for the pathophysiology and treatment of basal ganglia disorders and drug addiction.

Original languageEnglish (US)
Pages (from-to)1468-1474
Number of pages7
JournalCurrent Pharmaceutical Design
Issue number15
StatePublished - May 2008
Externally publishedYes


  • Adenosine A receptor
  • Basal ganglia disorders
  • Dopamine D receptor
  • Drug addiction
  • G protein-coupled receptors
  • Receptor heteromers
  • Striatum

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)


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