A2A adenosine receptor ligand binding and signaling is allosterically modulated by adenosine deaminase

Eduard Gracia , Kamil Pérez-Capote , Estefania Moreno , Jana Bakešová , Josefa Mallol , Carme Lluis , Rafael Franco , Antoni Cortes , Vicent Casado , Enric I. Canela (1)

1 Biochemistry and Molecular Biology

Adenosine A2A receptors (A2AR) are highly enriched in the striatum, which is the main motor control CNS area. Bioluminescence resonance energy transfer (BRET) assays showed that A2AR homomers may act as cell surface adenosine deaminase (ADA; EC 3.5.4.4) binding proteins. ADA binding affected the quaternary structure of A2AR present on the cell surface. ADA binding to adenosine A2A receptors increased both, agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK 1/2 phosphorylation. Collectively, the results showed that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal adenosine A2A receptors.

Mots clés: Life Sciences

Eduard Gracia, Kamil Pérez-Capote, Estefania Moreno, Jana Bakešová, Josefa Mallol, et al.. A2A adenosine receptor ligand binding and signaling is allosterically modulated by adenosine deaminase. Biochemical Journal, 2011, 435 (3), pp.701-709. ⟨10.1042/BJ20101749⟩. ⟨hal-00586466⟩