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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194443
Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function.
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The physiological meaning of the coexpression of adenosine A2A receptors and group I metabotropic glutamate receptors in γ- aminobutyric acid (GABA)ergic striatal neurons is intriguing. Here we provide in vitro and in vivo evidence for a synergism between adenosine and glutamate based on subtype 5 metabotropic glutamate (mGluR5) and adenosine A2A (A2AR) receptor/receptor interactions. Colocalization of A2AR and mGluR5 at the membrane level was demonstrated in nonpermeabilized human embryonic kidney (HEK)-293 cells transiently cotransfected with both receptors by confocal laser microscopy. Complexes containing A2AR and mGluR5 were demonstrated by Western blotting of immunoprecipitates of either Flag-A2AR or hemagglutinin-mGluR5 in membrane preparations from cotransfected HEK-293 cells and of native A2AR and mGluR5 in rat striatal membrane preparations. In cotransfected HEK-293 cells a synergistic effect on extracellular signal-regulated kinase 1/2 phosphorylation and c-fos expression was demonstrated upon A2AR/mGluR5 costimulation. No synergistic effect was observed at the second messenger level (cAMP accumulation and intracellular calcium mobilization). Accordingly, a synergistic effect on c-fos expression in striatal sections and on counteracting phencyclidine-induced motor activation was also demonstrated after the central coadministration of A2AR and mGluR5 agonists to rats with intact dopaminergic innervation. The results suggest that a functional mGluR5/A2AR interaction is required to overcome the well-known strong tonic inhibitory effect of dopamine on striatal adenosine A2AR function.
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FERRÉ, Sergi, KARCZ-KUBICHA, Marzena, HOPE, Bruce t., POPOLI, Patrizia p., BURGUEÑO, Javier, GUTIERREZ, Angeles m., CASADÓ, Vicent, FUXE, Kjell, GOLDBERG, Steven r. g, LLUÍS I BISET, Carme, FRANCO FERNÁNDEZ, Rafael, CIRUELA ALFÉREZ, Francisco. Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function.. _Proceedings of the National Academy of Sciences of the United States of America - PNAS_. 2002. Vol. 99, núm. 18, pàgs. 11940-11945. [consulta: 7 de febrer de 2026]. ISSN: 0027-8424. [Disponible a: https://hdl.handle.net/2445/194443]