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

被引：112

作者：

Cristovao-Ferreira, Sofia ^{[1
,2
]}

Navarro, Gemma ^{[3
,4
]}

Brugarolas, Marc ^{[3
,4
]}

Perez-Capote, Kamil ^{[3
,4
]}

Vaz, Sandra H. ^{[1
,2
]}

Fattorini, Giorgia ^{[5
,6
]}

Conti, Fiorenzo ^{[5
,6
,7
]}

Lluis, Carmen ^{[3
,4
]}

Ribeiro, Joaquim A. ^{[1
,2
]}

McCormick, Peter J. ^{[3
,4
]}

Casado, Vicent ^{[3
,4
]}

Franco, Rafael ^{[3
,4
,8
]}

Sebastiao, Ana M. ^{[1
,2
]}

机构：

[1] Univ Lisbon, Fac Med, Inst Pharmacol & Neurosci, P-1649028 Lisbon, Portugal

[2] Univ Lisbon, Inst Mol Med, Unit Neurosci, P-1649028 Lisbon, Portugal

[3] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain

[4] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain

[5] Univ Politecn Marche, Dept Neurosci, Ancona, Italy

[6] INRCA IRCCS, Ctr Neurobiol Aging, Ancona, Italy

[7] Univ Politecn Marche, Fdn Med Mol, Ancona, Italy

[8] Univ Navarra, CIMA, Lab Cell & Mol Neuropharmacol, Neurosci Div, E-31080 Pamplona, Spain

来源：

PURINERGIC SIGNALLING | 2013年 / 9卷 / 03期

关键词：

Adenosine heteromers; G protein coupling; GABA transporters; Astrocytes; PLASMA-MEMBRANE TRANSPORTER; ADENOSINE RECEPTORS; NEUROMUSCULAR-JUNCTION; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; OPIOID RECEPTORS; CEREBRAL-CORTEX; ATP RELEASE; ACTIVATION; A(2A);

D O I：

10.1007/s11302-013-9364-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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 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.

引用

页码：433 / 449

页数：17

共 43 条

[1]

LONG-TERM POTENTIATION AND NMDA RECEPTORS IN RAT VISUAL-CORTEX [J].