Extracellular adenosine 5 inch-triphosphate (ATP) is a key signaling molecule present in the central nervous system (CNS), and now is receiving greater attention due to its role as a messenger in the CNS during different physiological and pathological events. ATP is released into the extracellular space through vesicular exocytosis or from damaged and dying cells. Once in the extracellular environment, ATP binds to the specific receptors termed P2, which mediate ATP effects and are present broadly in both neurons and glial cells. There are P2X, the ligand-gated ionotropic receptors, possessing low affinity for ATP and responsible for fast excitatory neurotransmission, and P2Y, the metabotropic G-protein-coupled receptors, possessing high affinity for ATP. Since massive extracellular release of ATP often occurs after stress, brain ischemia and trauma, the extracellular ATP is considered relating to or involving in the pathological processes of many nervous system diseases. Conversely, the trophic functions have also been extensively described for the extracellular ATP. Therefore, extracellular ATP plays a very complex role in the CNS and its binding to P2 receptors can be related to toxic and/or beneficial effects. In this review, we described the extracellular ATP acting via P2 receptors as a potent therapeutic target for treatment of nervous system diseases.
在中枢神经系统中, 胞外ATP 是一种重要的信号转导分子, 目前, 它在中枢神经系统中的生理及病理作用已经得到了广泛的关注。 ATP可以通过囊泡胞吐形式被相关神经细胞释放到细胞外, 也可以因为细胞的损伤被直接释放出来。 在细胞外环境中, ATP 可以结合到它的特异性P2 受体上, 从而介导各种作用。 P2 受体有P2X 和P2Y 两种类型, 其中P2X 型受体是一类配体门控型的离子通道型受体, 这类受体对ATP的亲和力较低, 介导快速神经传递作用; P2Y 型受体是一类与代谢相关的G蛋白耦联受体, 对ATP的亲和力高。 由于大规模的ATP外释现象一般出现在各类应激、 脑缺血、 脑损伤之后, 因此细胞外ATP 被认为参与了神经系统疾病的病理过程。 但是, 大量报道也指出了细胞外ATP的营养功能。 因此, 可以认为细胞外ATP在中枢神经系统中扮演着非常复杂的角色, 结合特异性P2受体后, 可以引发有害性或有益性的结果。 本综述着重叙述了细胞外ATP作为神经系统疾病治疗靶点的潜能。