Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.
Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.
复制标题
乙醇差异调节BV2小胶质细胞中的P2X4和P2X7受体活性和功能。
DOI：
10.1016/j.neuropharm.2017.09.030
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发表时间：
2018-01
影响因子：
4.7
通讯作者：
Davies DL
中科院分区：
文献类型：
--
作者：
Asatryan L;Ostrovskaya O;Lieu D;Davies DL
神经炎症是慢性酒精暴露导致神经退行性脑损伤的机制之一。小胶质细胞在对环境损伤（包括乙醇）的先天性免疫反应的发展中发挥重要作用。三磷酸腺苷（ATP）激活的嘌呤能P2 X受体（P2 XR）亚型P2 X4 Rs和P2 X7 Rs在小胶质细胞中内源性表达并可调节其活性。这两种P2 XR亚型在结构和功能上不同：1）P2 X4 R在较低的水平被激活，（≤0.1 mM），而P2 X7 Rs-在较高浓度下（≥1.0 mM）ATP浓度; 2）P2 X4 R激活有助于脑源性神经营养因子的释放，并证实其在触觉异常性疼痛和神经病理性疼痛中的作用; 3）由于其在促炎性IL-1β的分泌中的作用，P2 X7 R已经涉及神经退行性病理、疼痛和吗啡耐受的发展。到目前为止，个别P2 XR亚型在乙醇对小胶质细胞的影响和功能后果中的作用尚未完全了解。基于P2 X4 Rs和P2 X7 Rs之间药理学和功能差异的现有知识，本工作测试了P2 X4 Rs和P2 X7 Rs在小胶质细胞中乙醇作用中发挥差异作用的假设。使用鼠BV 2小胶质细胞测定乙醇对P2 X4 R和P2 X7 R活性、表达和功能后果的影响。乙醇（≥100 mM）抑制P2 X4 R，但对P2 X7通道活性无活性。乙醇（25，100 mM）抑制P2 X4 R介导的小胶质细胞迁移，而它增强孔形成P2 X7 Rs。此外，乙醇（25，100 mM）增强P2 X7 R介导的BV 2小胶质细胞分泌IL-1β。乙醇还诱导两种P2 XR亚型的蛋白表达。总的来说，研究结果确定了P2 X4 Rs和P2 X7 Rs在乙醇对小胶质细胞影响方面的不同作用，这可能与乙醇暴露的不同阶段有关。
Neuroinflammation is one of the mechanisms leading to neurodegenerative brain damage induced by chronic alcohol (ethanol) exposure. Microglia play a major role in the development of innate immune responses to environmental injuries including ethanol. Adenosine 5″-triphosphate (ATP)-activated purinergic P2X receptor (P2XR) subtypes, P2X4Rs and P2X7Rs, are endogenously expressed in microglia and can modulate their activity. These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0.1 mM) whereas P2X7Rs – at higher (≥1.0 mM) ATP concentrations; 2) P2X4R activation contributes to the release of brain derived neurotrophic factor and its role in tactile allodynia and neuropathic pain is demonstrated; 3) Due to its role in the secretion of pro-inflammatory IL-1β, P2X7Rs have been implicated in the development of neurodegenerative pathologies, pain and morphine tolerance. To date, the roles of individual P2XR subtypes in ethanol effects on microglia and the functional consequences are not completely understood. Based on the existing knowledge on the pharmacological and functional differences between P2X4Rs and P2X7Rs, the present work tested the hypothesis that P2X4Rs and P2X7Rs play differential roles in ethanol action in microglia. Effects of ethanol on P2X4R and P2X7R activity, expression and functional consequences were determined using murine BV2 microglial cells. Ethanol (≥100 mM) inhibited P2X4Rs but was inactive on P2X7 channel activity. Ethanol (25, 100 mM) inhibited P2X4R-mediated microglia migration whereas it potentiated pore formation in P2X7Rs. Furthermore, ethanol (25, 100 mM) potentiated P2X7R-mediated IL-1β secretion from BV2 microglia. Ethanol also induced protein expression for both P2XR subtypes. Overall, the findings identify differential roles for P2X4Rs and P2X7Rs in regards to ethanol effects on microglia which may be linked to different stages of ethanol exposure.
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影响因子：
4.3
作者：
Franklin KM;Asatryan L;Jakowec MW;Trudell JR;Bell RL;Davies DL
通讯作者：
Davies DL
DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
影响因子：
7.3
作者：
Donnelly-Roberts, Diana L.;Namovic, Marian T.;Jarvis, Michael F.
通讯作者：
Jarvis, Michael F.
影响因子：
5.3
作者：
Alfonso-Loeches, Silvia;Pascual-Lucas, Maya;Guerri, Consuelo
通讯作者：
Guerri, Consuelo
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
影响因子：
4.7
作者：
Gendron, FP;Chalimoniuk, M;Sun, GY
通讯作者：
Sun, GY