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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
Other authors:	Universitat de Barcelona
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.
Subject(s):	-Adenosina -Neurotransmissors -Adenosine -Neurotransmitters
Rights:	cc-by-nc-sa (c) Ciruela Alférez, Francisco et al., 2006 http://creativecommons.org/licenses/by-nc-sa/3.0/es
Document type:	Article Article - Published version
Published by:	The Society for Neuroscience
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