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Glia. 2013 Jan;61(1):47-54. doi: 10.1002/glia.22358. Epub 2012 Jun 1.

Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors.

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Department of Neuropharmacology, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.


Microglia are sensitive to environmental changes and are immediately transformed into several phenotypes. For such dynamic "modal shifts", purinergic receptors have central roles. When microglia sense ATP/ADP leaked from injured cells by P2Y(12) receptors, they are transformed into a moving phenotype, showing process extension and migration toward the injured sites. Microglia upregulate adenosine A(2A) receptors, by which they retract the processes showing an amoeboid-shaped, activated phenotype. Microglia also upregulate P2Y(6) receptors, and if they meet UDP leaked from dead cells, microglia start to engulf and eat the dead cells as a phagocytic phenotype. The P2Y(12) receptor-mediated responses are modulated by other P2 or P1 receptors. In contrast, the P2Y(6) receptor-mediated responses were not influenced by P2Y(12) receptors and vice versa. Microglia appear to use purinergic signals either cooperatively or distinctively to cause their modal shifts.

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