[Gliotransmitter ATP-mediated cell-to-cell communication]

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.