2003
DOI: 10.1038/sj.npp.1300181
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The Human D2 Dopamine Receptor Synergizes with the A2A Adenosine Receptor to Stimulate Adenylyl Cyclase in PC12 Cells

Abstract: The adenosine A 2A receptor and the dopamine D 2 receptor are prototypically coupled to G s and G i /G o , respectively. In striatal intermediate spiny neurons, these receptors are colocalized in dendritic spines and act as mutual antagonists. This antagonism has been proposed to occur at the level of the receptors or of receptor-G protein coupling. We tested this model in PC12 cells which endogenously express A 2A receptors. The human D 2 receptor was introduced into PC12 cells by stable transfection. A 2A -a… Show more

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Cited by 49 publications
(37 citation statements)
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“…Adenosine may itself be beneficial for tumour cells as it can suppress the activity of inflammatory cells and also stimulate the local production of endothelial cells and subsequent angiogenesis. The actions of the A 2A R can be further complicated via possible synergism with dopamine D2 receptors [37]; whether this actually occurs in NET cells is not known but D2 receptors are co-expressed with somatostatin 2 and 5 receptors [38].…”
Section: Discussionmentioning
confidence: 99%
“…Adenosine may itself be beneficial for tumour cells as it can suppress the activity of inflammatory cells and also stimulate the local production of endothelial cells and subsequent angiogenesis. The actions of the A 2A R can be further complicated via possible synergism with dopamine D2 receptors [37]; whether this actually occurs in NET cells is not known but D2 receptors are co-expressed with somatostatin 2 and 5 receptors [38].…”
Section: Discussionmentioning
confidence: 99%
“…It must also be pointed out that some studies suggest that A 2A and D 2 receptor can interact synergistically, with stimulation of D 2 receptors potentiating the effects of A 2A receptor stimulation. These conditions seem to depend on the isoform of adenylyl cyclase involved or on the interruption of a previous long-term exposure to D 2 receptor agonists (Yao et al, 2002;Kudlacek et al, 2003;Vortherms and Watts, 2004). In any case, the main isoform of adenylyl cyclase in the striatum is AC5, and co-stimulation of G s -and G i -coupled receptors shows antagonistic interactions at the AC5 level (Chern, 2000;Defer et al, 2000).…”
Section: Discussionmentioning
confidence: 99%
“…It is now recognized that intramembrane receptor interactions constitute a common biochemical characteristic of receptor heteromers [14,[23][24][25]. The antagonistic A 2A -D 2 intramembrane receptor interaction has been repeatedly reported by different research groups in membrane preparations from different transfected cell lines and from human and rat striatum [28][29][30][31][32][33][34]. In these membrane preparations, the addition of a selective A 2A receptor agonist decreases the ability of dopamine (or a D 2 receptor agonist) to displace the binding of a selective D 2 receptor radioligand [28][29][30][31][32][33][34] (Fig.…”
Section: The Antagonistic a 2a -D 2 Intramembrane Recep-tor Interactionmentioning
confidence: 93%
“…Under some conditions, a synergistic A 2A -D 2 receptor interaction can also be detected [34,62], which seems to depend on the presence of an activator of G protein signaling (AGS3), which facilitates a synergistic interaction between G s/olf -and G i/o -coupled receptors on the activation of types II/IV adenylyl cyclase (ACII/IV) (reviewed in ref. 63).…”
Section: The Synergistic a 2a -D 2 Receptor Interaction At The G Protmentioning
confidence: 99%