Extracellular ATP or ADP Induce Chemotaxis of Cultured Microglia through Gi/o-Coupled P2Y Receptors
Open accessAbstract
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.
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P2Y12 is selectively expressed in non-activated microglia.
“we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [22]
P2Y12 is highly sensitive to adenosine diphosphate.
“P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [22]
P2Y12 elicits rapid and pronounced chemotactic responses of microglial processes.
“P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [22]
P2Y12 is rapidly downregulated following initiation of inflammation.
“P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [22]
P2Y12 mediates process motility during early injury responses.
“we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses.”
From Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex (2016) · cites this paper as [22]
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- Authors
- Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K., & Kohsaka, S.
- Affiliations
- National Institute of Neuroscience (JP)
- National Institute of Health Sciences (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-03-15
- Volume
- 21
- Issue
- 6
- Pages
- 1975-1982
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762617
- OpenAlex
- W1947551305
- Cited by
- 561
- References
- 58
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 17 · 2023: 22 · 2022: 22 · 2021: 18 · 2020: 17 · 2019: 16 · 2018: 13 · 2017: 19 · 2016: 28 · 2015: 25 · 2014: 29 · 2013: 39 · 2012: 41
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- microglia, chemotaxis, extracellular ATP, ADP, P2Y receptors, G protein-coupled receptors, Rac GTPase, ruffles, chemokinesis, purinergic signaling, pertussis toxin, suramin, brain injury, neuroinflammation
- MeSH terms
- Adenosine Diphosphate, Adenosine Monophosphate, Adenosine Triphosphate, Animals, Cell Membrane, Cells, Cultured, Chemotaxis, Extracellular Space, Virulence Factors, Bordetella, Diffusion Chambers, Culture, Rats, Wistar, Microglia, Receptors, Purinergic P2, GTP-Binding Proteins, GTP-Binding Protein alpha Subunits, Gi-Go, rac GTP-Binding Proteins, Heterotrimeric GTP-Binding Proteins, Pertussis Toxin, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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