P2X7 nucleotide receptor activation enhances IFNγ-induced type II nitric oxide synthase activity in BV-2 microglial cells
P2X7 nucleotide receptor activation enhances IFNγ-induced type II nitric oxide synthase activity in BV-2 microglial cells
复制标题
激活 P2X7 核苷酸受体可增强 IFNδ³诱导的 BV-2 小胶质细胞中 II 型一氧化氮合酶的活性
DOI：
10.1046/j.1471-4159.2003.01995.x
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发表时间：
2003-10-01
影响因子：
4.7
通讯作者：
Sun, GY
中科院分区：
文献类型：
--
作者：
Gendron, FP;Chalimoniuk, M;Sun, GY
在正常和病理条件下，脑细胞释放核苷酸，由于 P2 核苷酸受体的激活而调节多种细胞反应。在本研究中，研究了细胞外核苷酸对小鼠 BV-2 小胶质细胞中 IFNγ 诱导的 NO 释放的影响。 BV-2 细胞表达代谢型 P2Y 和离子型 P2X 受体的 mRNA。在测试的 P2 受体激动剂中，ATP、ADP、2',3'-O-(4-苯甲酰苯甲酰基)-ATP (BzATP) 和 2-甲硫基-ATP (2-MeSATP)（而非 UTP）增强 IFNγ 诱导的 iNOS 表达和 NO 产生，表明尿苷核苷酸受体 P2Y(2) 和 P2Y(6) 不参与此反应。 U0126 是 MEK1/2 的拮抗剂，MEK1/2 是一种磷酸化细胞外信号调节激酶 ERK1/2 的激酶，可减少 IFNγ 诱导的 NO 产生。 BzATP 是一种有效的 P2X(7) 受体激动剂，在增强 IFNgamma 诱导的 ERK1/2 磷酸化方面比 ATP、ADP 或 2-MeSATP 更有效。与 P2X(7) 受体的激活一致，高碘酸盐氧化的 ATP（一种 P2X(7) 受体拮抗剂）和苏拉明（一种非特异性 P2 受体拮抗剂）抑制 ATP 或 BzATP 对 IFNγ 诱导的 NO 产生的作用，而磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸 (PPADS)（几种 P2X 受体亚型的拮抗剂）则无效。这些结果表明，P2X(7) 受体的激活可能有助于神经退行性疾病中小胶质细胞的炎症反应。
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 IFNgamma-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 IFNgamma-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 IFNgamma-induced NO production. BzATP, a potent P2X(7) receptor agonist, was more effective than ATP, ADP, or 2-MeSATP at enhancing IFNgamma-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 IFNgamma-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.