Modulation of GABA transport by adenosine A 1R-A 2AR heteromers, which are coupled to both G s- and G i/o-Proteins

Sofia Cristóvão-Ferreira, Gemma Navarro, Marc Brugarolas, Kamil Pérez-Capote, Sandra H. Vaz, Giorgia Fattorini, Fiorenzo Conti, Carmen Lluis, Joaquim A. Ribeiro, Peter J. McCormick, Vicent Casadó, Rafael Franco, Ana M. Sebastião

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Abstract

Astrocytes play a key role in modulating synaptic transmission by controlling the available extracellular GABA via the GAT-1 and GAT-3 GABA transporters (GATs). Using primary cultures of rat astrocytes, we show here that an additional level of regulation of GABA uptake occurs via modulation of the GATs by the adenosine A 1 (A 1R) and A 2A (A 2AR) receptors. This regulation occurs through a complex of heterotetramers (two interacting homodimers) of A 1R-A 2AR that signal via two different G-proteins, G s and G i/o, and either enhances (A 2AR) or inhibits (A 1R) GABA uptake. These results provide novel mechanistic insight into how G-protein-coupled receptor heteromers signal. Furthermore, we uncover a previously unknown mechanism in which adenosine, in a concentration-dependent manner, acts via a heterocomplex of adenosine receptors in astrocytes to significantly contribute to neurotransmission at the tripartite (neuron-glia-neuron) synapse.

Original languageEnglish
Pages (from-to)15629-15639
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number44
DOIs
Publication statusPublished - Nov 2 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cristóvão-Ferreira, S., Navarro, G., Brugarolas, M., Pérez-Capote, K., Vaz, S. H., Fattorini, G., Conti, F., Lluis, C., Ribeiro, J. A., McCormick, P. J., Casadó, V., Franco, R., & Sebastião, A. M. (2011). Modulation of GABA transport by adenosine A 1R-A 2AR heteromers, which are coupled to both G s- and G i/o-Proteins. Journal of Neuroscience, 31(44), 15629-15639. https://doi.org/10.1523/JNEUROSCI.2526-11.2011