Oligomerization of adenosine A2A and dopamine D2 receptors in living cells

An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors

“…We and other authors also found evidence for the existence of selective heteromerization of A 2A and D 2 receptors and A 1 and D 1 receptors in transfected cells [4,8,10,11] and found biochemical characteristics of these receptor heteromers, called "intramembrane receptor-receptor interactions" [9], which could also be identified in the striatum (reviewed in ref. 22), therefore demonstrating the existence of A 2A -D 2 and A 1 -D 1 receptor heteromers in the brain [14,24,25].…”

“…A 1 receptor is widely distributed in the brain, including the striatum, while A 2A receptor is mostly concentrated in the striatum [2,3]. It is becoming increasingly obvious that the modulatory role of adenosine in the striatum is related to the ability of A 1 and A 2A receptors to heteromerize with themselves and with other GPCRs, such as dopamine, glutamate, cannabinoid and ATP receptors [4][5][6][7][8][9][10][11][12][13][14]. The present review focuses on the role of one particular adenosine receptor heteromer, the one constituted by the A 2A and the dopamine D 2 receptor, which is already having important implications for the treatment of neuropathologies involving the striatum (see below).…”

Stimulation of Adenosine Receptors Selectively Activates Gene Expression in Striatal Enkephalinergic Neurons

“…A 2A and D 2 receptors form heteromeric complexes with reciprocal antagonistic interactions that regulate the function of the GABAergic enkephalinergic neurons (Ferré et al, 1991(Ferré et al, , 1993(Ferré et al, , 1997Agnati et al, 2003;Canals et al, 2003;Kamiya et al, 2003;Ciruela et al, 2004;Woods and Ferré, 2005). Stimulation of A 2A receptors decreases the affinity of D 2 receptors for agonists by means of an intramembrane interaction (Ferré et al, 1991), while stimulation of D 2 receptors inhibits A 2A receptor-induced activation of adenylyl-cyclase (Kull et al, 1999;Hillion et al, 2002).…”

“…This is due to the segregation of D 1 and D 2 receptors, whose activation stimulates and inhibits the function of GABAergic dynorphinergic and GABAergic enkephalinergic neurons, respectively (Gerfen, 2000). A 2A and D 2 receptors exert reciprocal antagonistic interactions that modulate the function of GABAergic enkephalinergic neurons (Ferré et al, 1993(Ferré et al, , 1997Agnati et al, 2003) and recent studies have demonstrated the ability of A 2A and D 2 receptors to heteromerize Kamiya et al, 2003;Ciruela et al, 2004;Woods and Ferré, 2005). A 2A and D 2 receptors are prototypical G s -and G i -coupled receptors, respectively, which play opposite effects on adenylyl-cyclase (Kull et al, 1999;Hillion et al, 2002;Lee et al, 2002).…”

Heteromeric Dopamine Receptor Signaling Complexes: Emerging Neurobiology and Disease Relevance

“…The A2-D2 heteromer, also identified by coimmunoprecipitation, was first shown in neuroblastoma cells (Hillion et al, 2002) and has since been shown to exist in living cells by FRET and BRET analysis (Canals et al, 2003;Kamiya et al, 2003). It has been suggested that the A1-D1 and A2-D2 heteromers have a discrete distribution in the basal ganglia, with selective expression along the striatonigral and stratopallidal pathways, respectively (Ferré et al, 2007;Franco et al, 2007;Fuxe et al, 2008), and functional studies indicate that these receptor complexes may be the molecular entities responsible, at least in part, for the antagonistic interactions between adenosine and dopamine receptors, functioning to uncouple the dopamine receptors from their respective G-proteins and dampen receptor signaling (Azdad et The ability of adenosine-dopamine receptor heteromerization to attenuate dopamine receptor function indicates that these receptor complexes are of relevance to dopamine transmission in the basal ganglia, and thus have a potential role in dopamine disorders.…”