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PMID:11245682

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Citation

Honda, S, Sasaki, Y, Ohsawa, K, Imai, Y, Nakamura, Y, Inoue, K and Kohsaka, S (2001) Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J. Neurosci. 21:1975-82

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 AR-C69931MX 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 G(i/o)-coupled P2Y receptors.

Links

PubMed

Keywords

Adenosine Diphosphate/metabolism; Adenosine Diphosphate/pharmacology; Adenosine Monophosphate/analogs & derivatives; Adenosine Monophosphate/pharmacology; Adenosine Triphosphate/metabolism; Adenosine Triphosphate/pharmacology; Animals; Cell Membrane/drug effects; Cell Membrane/ultrastructure; Cells, Cultured; Chemotaxis/drug effects; Diffusion Chambers, Culture; Extracellular Space/metabolism; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism; GTP-Binding Proteins/metabolism; Heterotrimeric GTP-Binding Proteins/metabolism; Microglia/cytology; Microglia/drug effects; Microglia/metabolism; Pertussis Toxin; Rats; Rats, Wistar; Receptors, Purinergic P2/metabolism; Virulence Factors, Bordetella/pharmacology; rac GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:P2RY1

NOT|involved_in

GO:0001774: microglial cell activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:P2RY2

NOT|involved_in

GO:0001774: microglial cell activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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