Review G protein-coupled receptor oligomerization and brain integration: Focus on adenosinergic transmission Francisco Ciruela a, ⁎ , Víctor Fernández-Dueñas a , Javier Llorente a , Dasiel Borroto-Escuela b , Maria L. Cuffí a , Lourdes Carbonell a , Silvia Sánchez a , Luigi F. Agnati c , Kjell Fuxe b , Carla I. Tasca d a Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain b Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden c IRCCS San Camillo Lido, 30100 Venezia, Italy d Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040‐900 Florianópolis, SC, Brazil ARTICLE INFO ABSTRACT Article history: Accepted 30 April 2012 Available online 7 May 2012 The control of glutamatergic corticostriatal transmission is essential for the induction and expression of plasticity mechanisms in the striatum, a phenomenon thickly regulated by G protein-coupled receptors (GPCRs). Interestingly, in addition to dopamine receptors, adenosine and metabotropic glutamate receptors also play a key role in striatal functioning. The existence of a supramolecular organization (i.e. oligomer) containing dopamine, adenosine and metabotropic glutamate receptors in the striatal neurons is now being widely accepted by the scientific community. Indeed, these oligomers may enhance the diversity and perfor- mance by which extracellular striatal signals are transferred to the G-proteins in the process of receptor transduction, and also may allow unpredictable receptor-receptor allosteric regulations. Overall, here we want to review how formations of adenosine, dopamine and metabotropic glutamate receptors-containing oligomers impinge into striatal functioning in both normal and pathological conditions. This article is part of a Special Issue entitled: Brain Integration. © 2012 Elsevier B.V. All rights reserved. Keywords: A 2A R D 2 R mGlu 5 R Oligomerization Brain integration Contents 1. Introduction .......................................................... 87 2. Adenosine receptors containing oligomers and adenosinergic transmission: an example of neurotransmitter and neuromodulator brain integration .......................................... 87 2.1. The A 1 R/A 2A R heterodimer .............................................. 88 2.2. Adenosine and dopamine receptors oligomerization ................................ 89 2.3. Adenosine and glutamate receptors oligomerization ................................ 90 BRAIN RESEARCH 1476 (2012) 86 – 95 ⁎ Corresponding author at: Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina-Bellvitge, Pavelló de Govern, Av. Feixa Llarga, s/n, 08907 L'Hospitalet del Llobregat, Barcelona, Spain. Fax: +34 934029082. E-mail address: fciruela@ub.edu (F. Ciruela). 0006-8993/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2012.04.056 Available online at www.sciencedirect.com www.elsevier.com/locate/brainres