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(1)R) and A(2A) (A(2A)R) receptors. This regulation occurs through a complex of heterotetramers (two interacting homodimers) of A(1)R-A(2A)R that signal via two different G-proteins, G(s) and G(i/o), and either enhances (A(2A)R) or inhibits (A(1)R) 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.

Modulation of GABA transport by adenosine A 1R-A 2AR heteromers, which are coupled to both G s- and G i/o-Proteins / Cristóvão Ferreira, Sofia; Navarro, Gemma; Brugarolas, Marc; Pérez Capote, Kamil; Vaz, Sandra H.; Fattorini, Giorgia; Conti, Fiorenzo; Lluis, Carmen; Ribeiro, Joaquim A.; Mccormick, Peter J.; Casadó, Vicent; Franco, Rafael; Sebastião, Ana M.. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 31:44(2011), pp. 15629-15639. [10.1523/JNEUROSCI.2526-11.2011]

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

FATTORINI, GIORGIA;CONTI, FIORENZO;
2011-01-01

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(1)R) and A(2A) (A(2A)R) receptors. This regulation occurs through a complex of heterotetramers (two interacting homodimers) of A(1)R-A(2A)R that signal via two different G-proteins, G(s) and G(i/o), and either enhances (A(2A)R) or inhibits (A(1)R) 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.
2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/237064
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