# name
Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers

# metadata.dc.contributor.author[].value
Rodrigues Sepúlveda Marques, Ricardo Jorge

# metadata.dc.contributor.author[].value
Canela Campos, Enric I. (Enric Isidre), 1949-

# metadata.dc.description.abstract[].value
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.

# metadata.dc.rights[].value
cc-by-nc-sa (c) Ciruela Alférez, Francisco et al., 2006

# metadata.dc.source[].value
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

# metadata.dc.title[].value
Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers