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2002

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/194443

Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function.

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https://doi.org/10.1073/pnas.172393799

Abstract

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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Adenosina, Adenina, Dopamina, Neurotransmissors

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Adenosine, Adenine, Dopamine, Neurotransmitters

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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FERRÉ, Sergi, et al. 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, num. 18, pags. 11940-11945. ISSN 0027-8424. [consulted: 15 of June of 2026]. Available at: https://hdl.handle.net/2445/194443

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