Adenosine A_2A-dopamine D₂ receptor-receptor heteromers. Targets for neuro-psychiatric disorders

Emerging evidence shows that G protein-coupled receptors can form homo- and heteromers. These include adenosine A_2A 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 A_2A receptor-dopamine D ₂ receptor interactions. Recent results at the molecular level show that A_2A receptor-dopamine D₂ receptor heteromers represent the first example of epitope-epitope electrostatic interaction underlying receptor heteromerization. Most probably A_2A 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.