A1R-A2AR Heteromers Coupled to Gs and G I/0 Proteins Modulate GABA Transport into Astrocytes

Overview

Journal Purinergic Signal

Publisher Springer

Date 2013 May 10

PMID 23657626

Citations 66

Authors

Sofia Cristovao-Ferreira

Gemma Navarro

Marc Brugarolas

Kamil Perez-Capote

Sandra H Vaz

Giorgia Fattorini

Fiorenzo Conti

Carmen Lluis

Joaquim A Ribeiro

Peter J McCormick

Vicent Casado

Rafael Franco

Ana M Sebastiao

Affiliations

Soon will be listed here.

Abstract

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 A1 (A1R) and A2A (A2AR) receptors. This regulation occurs through A1R-A2AR heteromers that signal via two different G proteins, Gs and Gi/0, and either enhances (A2AR) or inhibits (A1R) 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.

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