A1R–A2AR heteromers coupled to Gs and Gi/0 proteins modulate GABA transport into astrocytes

Purinergic Signalling

Giorgia Fattorini⁴  Marc Brugarolas¹  Vicent Casadó¹  Sandra H. Vaz²  Joaquim A. Ribeiro²  Gemma Navarro¹  Peter J. McCormick¹  Ana M. Sebastião²  Rafael Franco³  Sofia Cristóvão-Ferreira²  Carmen Lluis¹  Fiorenzo Conti⁵  Kamil Pérez-Capote¹ 

[1] University of Barcelona$$University of Barcelona$$;University of Lisbon$$University of Lisbon$$;University of Barcelona$$University of Barcelona$$University of Navarra$$;Università Politecnica delle Marche$$INRCA IRCCS$$;Università Politecnica delle Marche$$INRCA IRCCS$$Università Politecnica delle Marche$$

关键词: Astrocytes;   

DOI  :  10.1007/s11302-013-9364-5

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

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 A_2A (A_2AR) receptors. This regulation occurs through A₁R–A_2AR heteromers that signal via two different G proteins, G_s and G_i/0, and either enhances (A_2AR) 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.

【 授权许可】

Unknown