A(1)R-A(2A)R heteromers coupled to G(s) and G(i/0) proteins modulate GABA transport into astrocytes

作者：Cristovao Ferreira Sofia; Navarro Gemma; Brugarolas Marc; Perez Capote Kamil; Vaz Sandra H; Fattorini Giorgia; Conti Fiorenzo; Lluis Carmen; Ribeiro Joaquim A; McCormick Peter J; Casado Vicent; Franco Rafael; Sebastiao Ana M^*

来源：Purinergic Signalling, 2013, 9(3): 433-449.

DOI：10.1007/s11302-013-9364-5

• Adenosine heteromers
• G protein coupling
• GABA transporters
• Astrocytes

Astrocytes play a key role in modulating synaptic transmission by controlling extracellular gamma-aminobutyric acid (GABA) levels via GAT-1 and GAT-3 GABA transporters (GATs). Using primary cultures of rat astrocytes, we show here that a further 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(1)R-A(2A)R heteromers that signal via two different G proteins, G(s) and G(i/0), and either enhances (A(2A)R) or inhibits (A(1)R) GABA uptake. These results provide novel mechanistic insight into how GPCR heteromers signal. Furthermore, we uncover a previously unknown mechanism where 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.

• 出版日期2013-9