A1R-A2AR 异源二聚体与 Gs 和 G i/0 蛋白偶联，调节 GABA 向星形胶质细胞的转运。
A1R-A2AR heteromers coupled to Gs and G i/0 proteins modulate GABA transport into astrocytes.
机构信息
Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, Edificio Egas Moniz, 1649-028, Lisbon, Portugal.
出版信息
Purinergic Signal. 2013 Sep;9(3):433-49. doi: 10.1007/s11302-013-9364-5. Epub 2013 May 10.
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.
摘要
星形细胞通过 GAT-1 和 GAT-3 GABA 转运体（GATs）控制细胞外 γ-氨基丁酸（GABA）水平，从而在调节突触传递中发挥关键作用。在这里，我们使用大鼠星形细胞的原代培养物表明，通过腺苷 A1（A1R）和 A2A（A2AR）受体对 GATs 的调节发生在 GABA 摄取的进一步水平上。这种调节通过通过两种不同的 G 蛋白 Gs 和 Gi/0 进行信号转导的 A1R-A2AR 异源二聚体发生，并且增强（A2AR）或抑制（A1R）GABA 摄取。这些结果为 GPCR 异源二聚体如何信号提供了新的机制见解。此外，我们揭示了一种以前未知的机制，即腺苷以浓度依赖的方式通过星形细胞中的腺苷受体异源复合物发挥作用，从而显著促进三突触（神经元-神经胶质-神经元）突触的神经传递。
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