title: Adenosine A2A-dopamine D2 receptor-receptor heteromers. Targets for neuro-psychiatric disorders.
abstract: 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.
authors.affiliation: National Institute on Drug Abuse, IRP, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Meritxell
authors.initials: M
authors.lastname: Canals
authors.forename: Daniel
authors.initials: D
authors.lastname: Marcellino
authors.forename: Javier
authors.initials: J
authors.lastname: Burgueno
authors.forename: Vicent
authors.initials: V
authors.lastname: Casadó
authors.forename: Joëlle
authors.initials: J
authors.lastname: Hillion
authors.forename: Maria
authors.initials: M
authors.lastname: Torvinen
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
authors.forename: Piero de
authors.initials: Pd
authors.lastname: Benedetti Pd
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Michel
authors.initials: M
authors.lastname: Bouvier
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Amina
authors.initials: A
authors.lastname: Woods
mesh_terms: 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*
chemical_list: D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2