A1R-A2AR heteromers coupled to Gs and Gi/0 proteins modulate GABA transport into astrocytes
A1R-A2AR heteromers coupled to Gs and Gi/0 proteins modulate GABA transport into astrocytes
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DOI：
10.1007/s11302-013-9364-5
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Sebastiao, Ana M.
中科院分区：
文献类型：
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作者：
Cristovao-Ferreira, Sofia;Navarro, Gemma;Sebastiao, Ana M.
星形胶质细胞通过GAT-1和GAT-3转运蛋白(GAT)控制细胞外GABA水平，在调节突触传递中起关键作用。利用原代培养的大鼠星形胶质细胞，我们证明了GABA摄取的进一步调节是通过腺苷A(1)(A(1)R)和A(2A)(A(2A)R)受体对GATS的调节而发生的。这种调节通过A(1)R-A(2A)R异构体发生，它通过两种不同的G蛋白G(S)和G(I/0)传递信号，并促进(A(2A)R)或抑制(A(1)R)GABA摄取。这些结果为GPCR异构体如何发出信号提供了新的机制洞察。此外，我们发现了一个先前未知的机制，即腺苷以一种浓度依赖的方式，通过星形胶质细胞中腺苷受体的异质复合体，显著促进三部分(神经元-神经胶质-神经元)突触的神经传递。
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.