Fig. 1.

Schematic representation of the role played by extracellular nucleosides and nucleotides in modulating cell-to-cell communication between neurons and glial cells in the central nervous system. ATP is exocytotically released from nerve terminals as a co-transmitter during synaptic transmission, and activates its pre- and post-synaptic receptors but also receptors on surrounding astrocytes and microglial cells. ADP and adenosine are generated through the activity of ecto-nucleotidases and further contribute to neurotransmission and to the modulation of glial cell functions. Astrocytes and microglia themselves can release ATP, which acts autocrinally or paracrinally on surrounding cells. An axonal non-vesicular ATP release has been recently identified, which plays a fundamental role in controlling oligodendrocyte myelinating functions, and, possibly, also NG2⁺ cell activity and maturation. No clear evidence for a vesicular release of uracil nucleotides is currently available, but pyrimidinergic receptors have been identified on any of the cell types shown here, thus indicating their important role in controlling glial activity. For the sake of clarity, only generic receptor families (i.e., P1, P2Y, and P2X) are shown. See text for details