Adenosine A2A-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 A2A receptor–dopamine D2 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 A2A 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 D2 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 A2A 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. [Copyright &y& Elsevier]