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Volume 7, Pages 74-85
Mini-Review Article

Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

1National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA
2Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain
3Department of Medical Sciences, Faculty of Medicine, University of Castilla-La Mancha, 02006 Albacete, Spain
4Department of Drug Research and Evaluation, Istituto Superiore di Sanita, 00161 Rome, Italy
5Center for Neuroscience of Coimbra, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
6Department of Biomedical Sciences, University of Modena and Reggio Emilia, 4100 Modena, Italy
7Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden

Received 7 June 2007; Revised 18 July 2007; Accepted 18 July 2007

Academic Editors: D. Shurtleff and S. Ferre

Copyright © 2007 Sergi Ferre et al.


By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS). Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit), where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.