Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors

Shizuyo Honda, Yo Sasaki, Keiko Ohsawa, Yoshinori Imai, Yasuko Nakamura, Kazuhide Inoue, Shinichi Kohsaka

Research output: Contribution to journalArticlepeer-review

456 Citations (Scopus)

Abstract

The initial microglial responses that occur after brain injury and in various neurological diseases are characterized by microglial accumulation in the affected sites of brain that results from the migration and proliferation of these cells. The early-phase signal responsible for this accumulation is likely to be transduced by rapidly diffusible factors. In this study, the possibility of ATP released from injured neurons and nerve terminals affecting cell motility was determined in rat primary cultured microglia. Extracellular ATP and ADP induced membrane ruffling and markedly enhanced chemokinesis in Boyden chamber assay. Further analyses using the Dunn chemotaxis chamber assay, which allows direct observation of cell movement, revealed that both ATP and ADP induced chemotaxis of microglia. The elimination of extracellular calcium or treatment with pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid, suramin, or adenosine-3′-phosphate-5′-phosphosulfate did not inhibit ATP- or ADP-induced membrane ruffling, whereas ARC69931MX or pertussis toxin treatments clearly did so. As an intracellular signaling molecule underlying these phenomena, the small G-protein Rac was activated by ATP and ADP stimulation, and its activation was also inhibited by pretreatment with pertussis toxin. These results strongly suggest that membrane ruffling and chemotaxis of microglia induced by ATP or ADP are mediated by Gi/o-coupled P2Y receptors.

Original languageEnglish
Pages (from-to)1975-1982
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number6
DOIs
Publication statusPublished - Mar 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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