Inhibition of Astrocytic Glutamate Transporter and Stimulation of Glutamate Release from Astrocytes Mediated via an A_<2a> Adenosine Receptor/PKA Signaling Pathway

低浓度（10nM）腺苷通过A_<2a>腺苷受体/蛋白激酶A（PKA）信号通路促进海马神经传递，在缺乏星形细胞谷氨酸转运体GLT-1的小鼠中也获得类似的效果。腺苷对突触前末端或突触后膜传导的递质释放无影响。腺苷抑制GLT-1功能，即通过A_<2a>腺苷受体/PKA信号通路介导谷氨酸进入星形胶质细胞。此外，腺苷通过A_<2a>腺苷受体/PKA信号通路刺激星形胶质细胞释放囊状谷氨酸，而不依赖于谷氨酸转运体对谷氨酸的反向转运。腺苷还通过参与PKA激活的A_<2a>腺苷受体增强星形胶质细胞内Ca^<2+>浓度，可能是通过未知的细胞内钙储存释放囊泡Ca^<2+>，这可能触发谷氨酸释放。腺苷对星形胶质细胞谷氨酸转运体和星形胶质细胞谷氨酸释放的影响会引起突触间隙谷氨酸浓度的增加，从而对海马神经传递起促进作用。因此，本研究的结果可能代表了一种新的神经调节途径，通过A_<2a>腺苷受体/PKA信号通路介导星形细胞的贡献。

A low concentration(10nM) of adenosine facilitated hippocampal neurotransmission via an A_<2a> adenosine receptor/protein kinase A(PKA) signaling pathway, and a similar effect was obtained with mice lacking the astrocytic glutamate transporter GLT-1. Adenosine had no effect on transmitter release from presynaptic terminals or postsynaptic membrane conductances. Adenosine inhibited GLT-1 function, i.e., uptake of glutamate into astrocytes, as mediated via an A_<2a> adenosine receptor/PKA signaling pathway. Furthermore, adenosine stimulated vesicular glutamate release from astrocytes via an A_<2a> adenosine receptor/PKA signaling pathway, independently of reverse transport of glutamate by glutamate transporters. Adenosine also enhanced intracellular Ca^<2+> concentrations in astrocytes via A_<2a> adenosine receptors involving PKA activation, perhaps by vesicular Ca^<2+> release from an unknown intracellular calcium store, which may trigger glutamate release. The effects of adenosine on astrocytic glutamate transporters and astrocytic glutamate release would cause an increase in glutamate concentrations in the synaptic clefts, responsible for the facilitatory action on hippocampal neurotransmission. The results of the present study, thus, may represent a new neuromodulatory pathway with an astrocytic contribution mediated via an A_<2a> adenosine receptor/PKA signaling pathway.