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Metabotropic glutamate 1α and adenosine A1 receptors assemble into functionally interacting complexes
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Recently, evidence has emerged that seven transmembrane G protein-coupled receptors may be present as homo- and heteromers in the plasma membrane. Here we describe a new molecular and functional interaction between two functionally unrelated types of G protein-coupled receptors, namely the metabotropic glutamate type 1alpha (mGlu(1alpha) receptor) and the adenosine A1 receptors in cerebellum, primary cortical neurons, and heterologous transfected cells. Co-immunoprecipitation experiments showed a close and subtype-specific interaction between mGlu(1alpha) and A1 receptors in both rat cerebellar synaptosomes and co-transfected HEK-293 cells. By using transiently transfected HEK-293 cells a synergy between mGlu(1alpha) and A1 receptors in receptor-evoked [Ca(2+)](i) signaling has been shown. In primary cultures of cortical neurons we observed a high degree of co-localization of the two receptors, and excitotoxicity experiments in these cultures also indicate that mGlu(1alpha) and A1 receptors are functionally related. Our results provide a molecular basis for adenosine/glutamate receptors cross-talk and open new perspectives for the development of novel agents to treat neuropsychiatric disorders in which abnormal glutamatergic neurotransmission is involved.
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CIRUELA ALFÉREZ, Francisco, ESCRICHE, Marisol, BURGUEÑO, Javier, ANGULO, Ester, CASADÓ, Vicent, SOLOVIEV, Mikhail m., CANELA CAMPOS, Enric i. (enric isidre), MALLOL MONTERO, Josefa, CHAN, Wai-yee, LLUÍS I BISET, Carme, MCILHINNEY, R. a. jeffrey, FRANCO FERNÁNDEZ, Rafael. Metabotropic glutamate 1α and adenosine A1 receptors assemble into functionally interacting complexes. _Journal of Biological Chemistry_. 2001. Vol. 276, núm. 21, pàgs. 18345-18351. [consulta: 21 de gener de 2026]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/122235]