Storage and release of ATP from Astrocytes in culture
Storage and release of ATP from Astrocytes in culture
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DOI：
10.1074/jbc.m209454200
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发表时间：
2003-01-10
影响因子：
4.8
通讯作者：
Verderio, C
中科院分区：
文献类型：
--
作者：
Coco, S;Calegari, F;Verderio, C
ATP从星形胶质细胞中释放出来，并参与其中钙波的传播。神经元的ATP分泌是量子和钙依赖性的，但它已被认为是从星形胶质细胞释放ATP可能不是囊泡。在这里，我们报告说，除了所描述的基础ATP释放促进暴露于无钙介质，星形胶质细胞释放嘌呤的条件下，钙升高。诱发释放不受间隙连接阻断剂花生四烯酸和氟芬那酸，从而排除嘌呤流出通过连接蛋白半通道。蔗糖梯度分析表明，一部分ATP储存在分泌颗粒中，在那里它是积累下来的电化学质子梯度敏感的v-ATP酶抑制剂巴弗洛霉素A，ATP的释放是部分敏感的破伤风神经毒素，而谷氨酸释放从相同的中毒星形胶质细胞几乎完全受损。最后，代谢型谷氨酸受体的激活，强烈地唤起谷氨酸的释放，在促进嘌呤分泌方面只有轻微的效果。这些数据表明，星形胶质细胞集中ATP颗粒，并可能通过调节分泌途径释放它。他们还表明，ATP储存囊泡可能不同于含谷氨酸囊泡，从而打开了它们的胞吐调节不同的可能性。
ATP is released from astrocytes and is involved in the propagation of calcium waves among them. Neuronal ATP secretion is quantal and calcium-dependent, but it has been suggested that ATP release from astrocytes may not be vesicular. Here we report that, besides the described basal ATP release facilitated by exposure to calcium-free medium, astrocytes release purine under conditions of elevated calcium. The evoked release was not affected by the gap-junction blockers anandamide and flufenamic acid, thus excluding purine efflux through connexin hemichannels. Sucrose-gradient analysis revealed that a fraction of ATP is stored in secretory granules, where it is accumulated down an electrochemical proton gradient sensitive to the v-ATPase inhibitor bafilomycin A, ATP release was partially sensitive to tetanus neurotoxin, whereas glutamate release from the same intoxicated astrocytes was almost completely impaired. Finally, the activation of metabotropic glutamate receptors, which strongly evokes glutamate release, was only slightly effective in promoting purine secretion. These data indicate that astrocytes concentrate ATP in granules and may release it via a regulated secretion pathway. They also suggest that ATP-storing vesicles may be distinct from glutamate-containing vesicles, thus opening up the possibility that their exocytosis is regulated differently.