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Involvement of P2X~4~ and P2Y~12~ receptors in ATP‐induced microglial chemotaxis by Keiko Ohsawa; Yasuhiro Irino; Yasuko Nakamura; Chihiro Akazawa; Kazuhide Inoue; Shinichi Kohsaka is a Neuroscience article available to read on EtoBox.

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We previously reported that extracellular ATP induces membrane ruffling and chemotaxis of microglia and suggested that their induction is mediated by the Gi/o-protein coupled P2Y 12 receptor (P2Y 12 R). Here we report discovering that the P2X 4 receptor (P2X 4 R) is also involved in ATP-induced microglial chemotaxis. To understand the intracellular signaling pathway downstream of P2Y 12 R that underlies microglial chemotaxis, we examined the effect of two phosphatidylinositol 30-kinase (PI3K) inhibitors, wortmannin, and LY294002, on chemotaxis in a Dunn chemotaxis chamber. The PI3K inhibitors significantly suppressed chemotaxis without affecting ATP-induced membrane ruffling. ATP stimulation increased Akt phosphorylation in the microglia, and the increase was reduced by the PI3K inhibitors and a P2Y 12 R antagonist. These results indicate that P2Y 12 R-mediated activation of the PI3K pathway is required for microglial chemotaxis in response to ATP. We also found that the Akt phosphorylation was reduced when extracellular calcium was chelated, suggesting that ionotropic P2X receptors are involved in microglial chemotaxis by affecting the PI3K pathway. We therefore tested the effect

Who reads Involvement of P2X~4~ and P2Y~12~ receptors in ATP‐induced microglial chemotaxis?

Author

Keiko Ohsawa; Yasuhiro Irino; Yasuko Nakamura; Chihiro Akazawa; Kazuhide Inoue; Shinichi Kohsaka

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square (ISSN 0894-1491)

Published

2007

Language

EN

Field

Neuroscience (Life Sciences)