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Title: Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers
Author: Ciruela Alférez, Francisco
Casadó, Vicent
Rodrigues, Ricardo J.
Luján, Rafael
Burgueño, Javier
Canals, Meritxell
Borycz, Janusz
Rebola, Nelson
Goldberg, Steven R.
Mallol Montero, Josefa
Cortés Tejedor, Antonio
Canela Campos, Enric I.
López-Giménez, Juan F.
Milligan, Graeme
Lluís i Biset, Carme
Cunha, Rodrigo A.
Ferré, Sergi
Franco Fernández, Rafael
Keywords: Adenosina
Issue Date: 15-Feb-2006
Publisher: The Society for Neuroscience
Abstract: The functional role of heteromers of G-protein-coupled receptors is a matter of debate. In the present study, we demonstrate that heteromerization of adenosine A1 receptors (A1Rs) and A2A receptors (A2ARs) allows adenosine to exert a fine-tuning modulation of glutamatergic neurotransmission. By means of coimmunoprecipitation, bioluminescence and time-resolved fluorescence resonance energy transfer techniques, we showed the existence of A1R-A2AR heteromers in the cell surface of cotransfected cells. Immunogold detection and coimmunoprecipitation experiments indicated that A1R and A2AR are colocalized in the same striatal glutamatergic nerve terminals. Radioligand-binding experiments in cotransfected cells and rat striatum showed that a main biochemical characteristic of the A1R-A2AR heteromer is the ability of A2AR activation to reduce the affinity of the A1R for agonists. This provides a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release. Furthermore, it is also shown that A1R-A2AR heteromers constitute a unique target for caffeine and that chronic caffeine treatment leads to modifications in the function of the A1R-A2AR heteromer that could underlie the strong tolerance to the psychomotor effects of caffeine.
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It is part of: Journal of Neuroscience, 2006, vol. 26, num. 7, p. 2080-2087
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ISSN: 0270-6474
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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