Adenosine A(2A)-dopamine D-2 receptor-receptor heteromers. Targets for neuro-psychiatric disorders

Emerging evidence show; 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 D-2 receptor heteromers gives a frame for the well-known antagonistic interaction between both receptors, which is the bases for a new therapeutic approach for neuropsychiatric 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 D-2 receptor heteromers represent the first example of epitope-epitope electrostatic interaction underlying receptor heteromerization. Most probably A(2A) receptor-D-2 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 D-2 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.