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2006-02-15

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cc-by-nc-sa (c) Ciruela Alférez, Francisco et al., 2006
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/122382

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

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Recurs relacionat

https://doi.org/10.1523/JNEUROSCI.3574-05.2006

Resum

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.

Matèries

Adenosina, Neurotransmissors

Matèries (anglès)

Adenosine, Neurotransmitters

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

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), LÓPEZ-GIMÉNEZ, Juan f., MILLIGAN, Graeme, LLUÍS I BISET, Carme, CUNHA, Rodrigo a., FERRÉ, Sergi, FRANCO FERNÁNDEZ, Rafael. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. _Journal of Neuroscience_. 2006. Vol. 26, núm. 7, pàgs. 2080-2087. [consulta: 22 de gener de 2026]. ISSN: 0270-6474. [Disponible a: https://hdl.handle.net/2445/122382]

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