Prostaglandins stimulate calcium-dependent glutamate release in astrocytes
Prostaglandins stimulate calcium-dependent glutamate release in astrocytes
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DOI：
10.1038/34651
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发表时间：
1998-01-15
期刊：
影响因子：
64.8
通讯作者：
Volterra, A
中科院分区：
文献类型：
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作者：
Bezzi, P;Carmignoto, G;Volterra, A
大脑中的星形胶质细胞与神经元形成密切相关的网络。它们对神经元活动做出反应，并通过提高细胞内钙浓度（[Ca2+](i)）突触释放谷氨酸（1,2），这可能代表向神经元发送反向信号的开始（3-5）。本研究表明，星形胶质细胞上AMPA/kainate和代谢性谷氨酸受体（mGluRs）的共激活刺激这些细胞通过前列腺素介导的Ca2+依赖性过程释放谷氨酸。前列腺素合成的药理学抑制阻止谷氨酸释放，而前列腺素（特别是PGE(2)）的应用模仿并阻断了谷氨酸受体激动剂的释放作用。PGE(2)在抑制神经元胞外释放的条件下，促进培养星形胶质细胞和急性脑片中Ca2+依赖性谷氨酸的释放。当应用于CA1海马区时，PGE(2)诱导星形胶质细胞和神经元中[Ca2+](i)的增加。神经元中[Ca2+](i)的增加是由星形胶质细胞释放的谷氨酸介导的，因为它被谷氨酸拮抗剂所消除。我们的研究结果揭示了星形胶质细胞释放受调节的递质的新途径，并概述了神经元和星形胶质细胞之间存在一种完整的谷氨酸能串话，这种串话可能在突触可塑性和神经毒性中发挥关键作用。
Astrocytes in the brain form an intimately associated network with neurons. They respond to neuronal activity and synaptically released glutamate by raising intracellular calcium concentration ([Ca2+](i))(1,2), which could represent the start of back-signalling to neurons(3-5). Here we show that coactivation of the AMPA/kainate and metabotropic glutamate receptors (mGluRs) on astrocytes stimulates these cells to release glutamate through a Ca2+-dependent process mediated by prostaglandins. Pharmacological inhibition of prostaglandin synthesis prevents glutamate release, whereas application of prostaglandins (in particular PGE(2)) mimics and occludes the releasing action of GluR agonists. PGE(2) promotes Ca2+-dependent glutamate release from cultured astrocytes and also from acute brain slices under conditions that suppress neuronal exocytotic release. When applied to the CA1 hippocampal region, PGE(2) induces increases in [Ca2+](i) both in astrocytes and in neurons. The [Ca2+](i) increase in neurons is mediated by glutamate released from astrocytes, because it is abolished by GluR antagonists. Our results reveal a new pathway of regulated transmitter release from astrocytes and outline the existence of an integrated glutamatergic cross-talk between neurons and astrocytes in situ that may play critical roles in synaptic plasticity and in neurotoxicity.