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http://hdl.handle.net/2445/194443
Title: | Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function. |
Author: | 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, Carme Franco Fernández, Rafael Ciruela Alférez, Francisco |
Keywords: | Adenosina Adenina Dopamina Neurotransmissors Adenosine Adenine Dopamine Neurotransmitters |
Issue Date: | 2002 |
Publisher: | National Academy of Sciences |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1073/pnas.172393799 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2002, vol. 99, num. 18, p. 11940-11945 |
URI: | http://hdl.handle.net/2445/194443 |
Related resource: | https://doi.org/10.1073/pnas.172393799 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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