Koizumi Shuichi, Fujishita Kayoko
Department of Pharmacology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanasi 409-3898, Japan.
Brain Nerve. 2007 Jul;59(7):707-15.
Much attention has focused on glial cells especially astrocytes because they are not simply supportive but are integrative, being able to receive inputs, assimilate information and send instructive chemical signals to other neighboring cells including neurons and vascular walls. So-called "gliotransmitter" has a central role for these events. Although at first, the excitatory neurotransmitter glutamate was found to be a major extracellular messenger, extracellular ATP has come into the limelight as an important extracellular messenger for these communications. Astrocytes express various neurotransmitter receptors including P2 receptors, release ATP in response to various stimuli and respond to extracellular ATP to cause various physiological responses. The intercellular communication "Ca2+ wave" in astrocytes was found to be mainly mediated by the release of ATP and the activation of P2 receptors, suggesting that ATP is a dominant "gliotransmitter" between astrocytes. Because neurons also express various P2 receptors and synapses are surrounded by astrocytes, astrocytic ATP could affect neuronal activities and even dynamically regulate synaptic transmission in adjacent neurons as if forming a "tripartite synapse". In addition, astrocytes also enwrap blood vessels by their endfeet. Pericytes are cells that are located at the abluminal side of capillaries with patchy structure, and face to astrocytic endfeet. They also express various P2 receptors and communicate with astrocytes by gliotransmitter ATP. In this review, we summarize the role of gliotrasnmitter ATP, as compared with glutamate, in regulation of adjacent cells such as astrocytes, neurons and capillaries. Dynamic communication between neurons, astrocytes and blood vessels mediated by ATP would be a key event in the processing or integration of information in the CNS.
许多注意力都集中在神经胶质细胞尤其是星形胶质细胞上，因为它们不仅具有支持作用，还具有整合功能，能够接收输入信号、同化信息并向包括神经元和血管壁在内的其他邻近细胞发送有指导意义的化学信号。所谓的“胶质递质”在这些过程中起着核心作用。虽然起初发现兴奋性神经递质谷氨酸是主要的细胞外信使，但细胞外ATP作为这些通讯的重要细胞外信使已备受关注。星形胶质细胞表达包括P2受体在内的各种神经递质受体，对各种刺激作出反应释放ATP，并对细胞外ATP作出反应以引起各种生理反应。星形胶质细胞中的细胞间通讯“Ca2+波”被发现主要由ATP的释放和P2受体的激活介导，这表明ATP是星形胶质细胞之间占主导地位的“胶质递质”。由于神经元也表达各种P2受体且突触被星形胶质细胞包围，星形胶质细胞的ATP可能影响神经元活动，甚至动态调节相邻神经元的突触传递，就好像形成了一个“三方突触”。此外，星形胶质细胞还通过其终足包裹血管。周细胞是位于毛细血管腔外侧、结构呈斑块状且面向星形胶质细胞终足的细胞。它们也表达各种P2受体，并通过胶质递质ATP与星形胶质细胞通讯。在这篇综述中，我们总结了与谷氨酸相比，胶质递质ATP在调节星形胶质细胞、神经元和毛细血管等相邻细胞中的作用。由ATP介导的神经元、星形胶质细胞和血管之间的动态通讯将是中枢神经系统信息处理或整合中的关键事件。
