Gi protein coupling to adenosine A1-A2A receptor heteromers in human brain caudate nucleus

Autor: Enric I. Canela, J. Javier Meana, Rafael Franco, Sergio Barrondo, Vicent Casadó, Carmen Lluis, Josefa Mallol, Milena Spasic, Joan Sallés, Antoni Cortés, Luis F. Callado
Rok vydání: 2010
Předmět:
Zdroj: Journal of Neurochemistry.
ISSN: 1471-4159
0022-3042
DOI: 10.1111/j.1471-4159.2010.06810.x
Popis: J. Neurochem. (2010) 114, 972–980. Abstract Pharmacological characterization of adenosine A1 and A2A receptors in human brain caudate nucleus membranes led to non-cooperative binding of radiolabelled ligands. In human caudate nucleus but not in cortex, the agonist binding to A1 receptors was modulated by the agonist binding to A2A receptors indicating a functional negative cross-talk. Accordingly, the A1 receptor-activation-mediated Gi-dependent guanosine 5′-o-(3-[35S]thio-triphosphate) binding was modulated by agonist binding to A2A receptors. A2A receptors occupation led to a decrease in the potency of A1 receptor agonists. These results indicate that A1 but not A2A receptors activation, likely occurring at low adenosine concentrations, engages a Gi-mediated signaling; however, when both receptors are occupied by adenosine, there is an A2A receptor-mediated impairment of Gi-operated transducing units. These findings are relevant to get insight into the complex relationships derived from co-expression of multiple neurotransmitter/neuromodulator receptors subtypes that individually are coupled to different G proteins. A further finding was the demonstration that the A2A receptor agonist, CGS 21680, at high concentrations able to significantly bind to the A1 receptor, behaved as a partial agonist of the later receptor. This fact might be taken into account when characterizing CGS 21680 actions in human cells expressing A1 receptors when the compound is used at micromolar concentrations.
Databáze: OpenAIRE
Externí odkaz: