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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors

Author(s): S. Ferre, C. Quiroz, A. S. Woods, R. Cunha, P. Popoli, F. Ciruela, C. Lluis, R. Franco, K. Azdad and S. N. Schiffmann

Volume 14, Issue 15, 2008

Page: [1468 - 1474] Pages: 7

DOI: 10.2174/138161208784480108

Price: $65


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 intramembrane 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 on Gs/olf- and Gi/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 Gs/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 of A2-D2 receptor interactions will have implications for the pathophysiology and treatment of basal ganglia disorders and drug addiction.

Keywords: Adenosine A2A Receptor, Dopamine D2 Receptor, G Protein-Coupled Receptors, Receptor Heteromers, Striatum, Basal Ganglia Disorders, Drug Addiction

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