Abstract
Glial cells are now recognized as important neuronal partners to regulate various brain functions. They release so-called "gliotransmitter" ATP or other nucleotides that control functions of neighboring cells including neurons, glial cells and vascular cells. In the present study, we show that astrocytes release nucleotides, by which they show both dynamic and static control of neuronal functions. Astrocytes release ATP in response to various stimuli or even spontaneously. Thus, astrocytes or adjacent cells including neurons receive ATP/P2 receptor-mediated signals in a tonic fashion. When incubated with P2 receptor antagonists or the ATP degrading enzyme apyrase, they alone dynamically affect neuronal activities. In addition, when incubated with these antagonist or apyrase for longer periods, expression of neurotransmitter receptors such as M1 muscarinic acetylcholine receptors in neurons were affected, which was totally dependent upon astrocytic nucleotides. Thus, astorocytes cause both dynamic and sustained change in neuronal activities by releasing gliotransmitter nucleotides. Astrcotyes also release uridine nucleotides that regulate vasculatures and microglial functions. We also discuss to differences between adenine and pyrimidine nucleotides for regulation of brain functions. Such wide-ranging regulation by astrocytic nucleotides may explain fine-tuning of complex brain functions. [J Physiol Sci. 2007;57 Suppl:S9]
