Modulation of GABA Transport by Adenosine A1R–A2AR Heteromers, Which Are Coupled to Both Gs- and Gi/o-Proteins

Autor:	Gemma Navarro, Carmen Lluis, Joaquim A. Ribeiro, Sandra H. Vaz, Fiorenzo Conti, Ana M. Sebastião, Sofia Cristóvão-Ferreira, Marc Brugarolas, Kamil Pérez-Capote, Rafael Franco, Vicent Casadó, Giorgia Fattorini, Peter J. McCormick
Rok vydání:	2011
Předmět:	General Neuroscience GTP-Binding Protein alpha Subunits Transporter Articles Neurotransmission Biology Adenosine Adenosine receptor Cell biology Synapse Biochemistry Extracellular medicine Receptor medicine.drug
Zdroj:	The Journal of Neuroscience. 31:15629-15639
ISSN:	1529-2401 0270-6474
Popis:	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 A1(A1R) and A2A(A2AR) receptors. This regulation occurs through a complex of heterotetramers (two interacting homodimers) of A1R–A2AR that signal via two different G-proteins, Gsand Gi/o, and either enhances (A2AR) or inhibits (A1R) 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02e42f8618c7eda6695dd2c36148dced https://doi.org/10.1523/jneurosci.2526-11.2011 Zobrazit plný text záznamu