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 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 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 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.
Ferré
Sergi
S
National Institute on Drug Abuse, IRP, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Ciruela
Francisco
F
Canals
Meritxell
M
Marcellino
Daniel
D
Burgueno
Javier
J
Casadó
Vicent
V
Hillion
Joëlle
J
Torvinen
Maria
M
Fanelli
Francesca
F
Benedetti Pd
Piero de
Pd
Goldberg
Steven R
SR
Bouvier
Michel
M
Fuxe
Kjell
K
Agnati
Luigi F
LF
Lluis
Carme
C
Franco
Rafael
R
Woods
Amina
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*
D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2