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P2X 7 nucleotide receptor activation enhances IFNγ‐induced type II nitric oxide synthase activity in BV‐2 microglial cells
Author(s) -
Gendron FernandPierre,
Chalimoniuk Malgorzata,
Strosznajder Joanna,
Shen Siming,
González Fernando A.,
Weisman Gary A.,
Sun Grace Y.
Publication year - 2003
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 - 10.1046/j.1471-4159.2003.01995.x
Subject(s) - ppads , p2y receptor , p2 receptor , receptor , suramin , biology , agonist , metabotropic receptor , receptor antagonist , extracellular , purinergic receptor , ionotropic effect , microbiology and biotechnology , biochemistry , endocrinology , medicine , antagonist , glutamate receptor
Under normal and pathological conditions, brain cells release nucleotides that regulate a wide range of cellular responses due to activation of P2 nucleotide receptors. In this study, the effect of extracellular nucleotides on IFNγ‐induced NO release in murine BV‐2 microglial cells was investigated. BV‐2 cells expressed mRNA for metabotropic P2Y and ionotropic P2X receptors. Among the P2 receptor agonists tested, ATP, ADP, 2′,3′‐O‐(4‐benzoylbenzoyl)‐ATP (BzATP), and 2‐methylthio‐ATP (2‐MeSATP), but not UTP, enhanced IFNγ‐induced iNOS expression and NO production, suggesting that the uridine nucleotide receptors P2Y 2 and P2Y 6 are not involved in this response. U0126, an antagonist for MEK1/2, a kinase that phosphorylates the extracellular signal‐regulated kinases ERK1/2, decreased IFNγ‐induced NO production. BzATP, a potent P2X 7 receptor agonist, was more effective than ATP, ADP, or 2‐MeSATP at enhancing IFNγ‐induced ERK1/2 phosphorylation. Consistent with activation of the P2X 7 receptor, periodate‐oxidized ATP, a P2X 7 receptor antagonist, and suramin, a non‐specific P2 receptor antagonist, inhibited the effect of ATP or BzATP on IFNγ‐induced NO production, whereas pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS), an antagonist of several P2X receptor subtypes, was ineffective. These results suggest that activation of P2X 7 receptors may contribute to inflammatory responses in microglial cells seen in neurodegenerative diseases.