Reciprocal interactions between adenosine A2A and dopamine D2 receptors in Chinese hamster ovary cells co-transfected with the two receptors

Kull, Björn; Ferré, Sergi; Arslan, Giulia; Svenningsson, Per; Fuxé, Kjell; Owman, Christer; Fredholm, Bertil B.

doi:10.1016/s0006-2952(99)00184-7

Cited by 114 publications

(116 citation statements)

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“…These were expected findings given the fact that GABAergic enkephalinergic neurons show the highest expression of A 2A receptors in the brain (Schiffmann et al, 1991;Hettinger et al, 2001). Adenosine A 2A receptors are Gs-olf protein-coupled receptors whose main signaling pathway is adenylyl-cyclase activation, the cAMP-PKA cascade (Kull et al, 1999(Kull et al, , 2000. Important PKA substrates include the dopamine and cyclic adenosine 3 0 ,5 0 -monophosphate-regulated phophoprotein, 32 kDa (DARPP-32) and the nuclear constitutive transcription factor cAMP response element binding protein (CREB) (Greengard et al, 1999).…”

Section: Discussionsupporting

confidence: 60%

“…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). By means of the strong antagonistic D 2 -A 2A receptor interaction at the adenylyl cyclase level, and due to the existence of a tonic effect of dopamine on D 2 receptors, under normal conditions A 2A receptors are practically unable to activate the cAMP-PKA signaling pathway (Agnati et al, 2003;Ferré et al, 2003Ferré et al, , 2004.…”

Section: Discussionmentioning

confidence: 99%

“…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). Stimulation of A 2A receptors can potentially stimulate striatal adenylyl-cyclase, with the consequent activation of the cAMP-PKA signaling pathway and the induction of the expression of different genes, such as c-fos and preproenkephalin (Agnati et al, 2003;Ferré et al, 2003Ferré et al, , 2004.…”

Section: Introductionmentioning

confidence: 99%

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

Karcz-Kubicha

Ferré

Diaz-Ruiz

et al. 2006

Neuropsychopharmacol

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In the striatum, adenosine A 2A and dopamine D 2 receptors exert reciprocal antagonistic interactions that modulate the function of GABAergic enkephalinergic neurons. We have previously shown that stimulation of adenosine A 1 receptors allows the stimulation of A 2A receptors to overcome a tonic inhibitory effect of D 2 receptors and induce striatal expression of c-fos. In the present work, by studying co-localization of c-Fos immunoreactivity and preproenkephalin and preprodynorphin transcripts, we show that co-administration of the A 1 receptor agonist CPA and the A 2A receptor agonist CGS 21680 increases the striatal expression of c-fos in GABAergic enkephalinergic but not in GABAergic dynorphinergic neurons. Co-administration of CPA and CGS 21680 also induced a significant increase in the striatal expression of preproenkephalin. The results underscore the role of adenosine in the activation of gene expression in the GABAergic enkephalinergic neuron.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Karcz-Kubicha

Ferré

Diaz-Ruiz

et al. 2006

Neuropsychopharmacol

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“…One of the first examples was the A 2A -D 2 heterodimer, where the binding of the adenosine A 2A agonist CGS-21680 lead to a reduction of the affinity of the high-affinity dopamine D 2 agonist binding site (Fuxe et al, 1998). In this RM, a reciprocal inter action between D 2 and A 2A receptors also exists, as D 2 receptor can inhibit the A 2A -induced increase in cyclic AMP (cAMP) accumulation via G i/o at the level of the adenylate cyclase (Kull et al, 1999). As discussed by Woods and Jackson (2013), in this heterodimer, the first step driving heteromerization involves the phosphorylation of the serine/threonine in an epitope containing a casein kinase 1/2-consensus site, and dopaminergic neurotransmission, through cAMP-dependent protein kinase A (PKA), slows down heteromerization.…”

Section: Rm and Vmnsmentioning

confidence: 99%

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Guidolin

Marcoli

Tortorella

et al. 2018

Reviews in the Neurosciences

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Abstract:The proposal of receptor-receptor interactions (RRIs) in the early 1980s broadened the view on the role of G protein-coupled receptors (GPCR) in the dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate not only as monomers but also as receptor complexes, in which the integration of the incoming signals depends on the number, spatial arrangement, and order of activation of the protomers forming the complex. The main biochemical mechanisms controlling the functional interplay of GPCR in the receptor complexes are direct allosteric interactions between protomer domains. The formation of these macromolecular assemblies has several physiologic implications in terms of the modulation of the signaling pathways and interaction with other membrane proteins. It also impacts on the emerging field of connectomics, as it contributes to set and tune the synaptic strength. Furthermore, recent evidence suggests that the transfer of GPCR and GPCR complexes between cells via the exosome pathway could enable the target cells to recognize/decode transmitters and/or modulators for which they did not express the pertinent receptors. Thus, this process may also open the possibility of a new type of redeployment of neural circuits. The fundamental aspects of GPCR complex formation and function are the focus of the present review article.

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“…Confocal analysis revealed high colocalization of both receptors (white color in Figure 2b, right panel). By coupling to G s-olf proteins, A 2A receptors stimulate adenylyl-cyclase and induce cAMP accumulation (Kull et al, 1999). On the other hand, CB 1 receptors couple to G i-o proteins, and inhibit adenylyl cyclase (Bidaut-Russell et al, 1990;Felder et al, 1995;Hillard et al, 1999 (Salim et al, 2000).…”

Section: A 2a -Cb 1 Receptor Heteromerization In Living Cellsmentioning

confidence: 99%

Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

Carriba

Ortiz

Patkar

et al. 2007

Neuropsychopharmacol

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219

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The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB 1 receptors, is still a matter of debate. In the present study, we report that CB 1 and adenosine A 2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB 1 receptor signaling was found to be completely dependent on A 2A receptor activation. Accordingly, blockade of A 2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB 1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A 2A and CB 1 receptors.

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Reciprocal interactions between adenosine A2A and dopamine D2 receptors in Chinese hamster ovary cells co-transfected with the two receptors

Cited by 114 publications

References 40 publications

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

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

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids

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