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

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 mean...

Descripción completa

Detalles Bibliográficos
Autores: Ciruela Alférez, Francisco, Casadó, Vicent, Rodrigues Sepúlveda Marques, Ricardo Jorge, Luján, Rafael, Burgueño, Javier, Canals Buj, Meritxell, Borycz, Janusz, Rebola, Nelson, Goldberg, Steven R., Mallol Montero, Josefa, Cortés Tejedor, Antonio, Canela Campos, Enric I. (Enric Isidre), 1949-, López-Giménez, Juan F., Milligan, Graeme, Lluís i Biset, Carme, Cunha, Rodrigo A., Ferré, Sergi, Franco Fernández, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2006
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122382
Acceso en línea:https://hdl.handle.net/2445/122382
Access Level:acceso abierto
Palabra clave:Adenosina
Neurotransmissors
Adenosine
Neurotransmitters
Descripción
Sumario: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.

Similares en LA Referencia