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Lysophosphatidic acid‐induced membrane ruffling and brain‐derived neurotrophic factor gene expression are mediated by ATP release in primary microglia
Author(s) -
Fujita Ryousuke,
Ma Yan,
Ueda Hiroshi
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05599.x
Subject(s) - lysophosphatidic acid , phospholipase c , pertussis toxin , microbiology and biotechnology , p2y receptor , membrane ruffling , autotaxin , receptor , microglia , apyrase , biology , neurotrophic factors , neuroglia , biochemistry , g protein , signal transduction , endocrinology , purinergic receptor , immunology , inflammation , cell , cytoskeleton , central nervous system
We examined the effects of lysophosphatidic acid (LPA) on microglia, which may play an important role in the development and maintenance of neuropathic pain. LPA caused membrane ruffling as detected by scanning electron microscopy, and increased the expression of brain‐derived neurotrophic factor (BDNF) in a primary culture of rat microglia, which express LPA 3 , but not LPA 1 or LPA 2 receptors. These actions were inhibited by a Gα q/11 ‐antisense oligodeoxynucleotide (AS‐ODN), U73122, an inhibitor of phospholipase C (PLC), and apyrase, which specifically degrades ATP and ADP. When ATP release was measured using a luciferin‐luciferase bioluminescence assay, LPA was shown to increase it in an LPA 3 and PLC inhibitor‐reversible manner. However, LPA‐induced ATP release was also blocked by the Gα q/11 AS‐ODN, but not by pertussis toxin. These results suggest that LPA induces the release of ATP from rat primary cultured microglia via the LPA 3 receptor, Gα q/11 and PLC, and that the released ATP or ectopically converted ADP may in turn cause membrane ruffling via P2Y 12 receptors and Gα i/o activation, and BDNF expression via activation of P2X 4 receptors.