Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: A calcium imaging study
Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: A calcium imaging study
复制标题
DOI：
10.1016/j.neuropharm.2011.05.019
复制
发表时间：
2011-09-01
影响因子：
4.7
通讯作者：
Hanani, Menachem
中科院分区：
文献类型：
--
作者：
Kushnir, Raya;Cherkas, Pavel S.;Hanani, Menachem
感觉神经节中的卫星胶质细胞（SGCs）由于神经损伤而在结构和生物化学上发生改变。虽然有足够的证据表明，P2嘌呤能受体在中央胶质细胞损伤后改变，有非常少的信息在SGCs类似的变化，虽然它是公认的SGCs被赋予P2受体。使用钙成像，我们的特点是在短期培养的小鼠三叉神经节SGCs中P2受体的变化。7天后，诱导的下颌下炎症与完全弗氏佐剂，有一个显着增加的敏感性SGCs ATP，与激活的阈值从5 μ M降低到10 nM。在眶下神经切断术后的完整三叉神经节中也观察到类似的结果。使用药理学工具，我们研究了这些变化在培养的SGCs的受体机制。我们发现，在对照组织中，ATP的反应是由P2 Y（代谢型）受体介导的，而炎症后的反应主要是由P2 X（离子型）受体介导的。由于排除了P2 X1、3、6受体的贡献，并且对P2 X7激动剂的敏感性在炎症后没有改变，因此似乎炎症后对ATP的反应主要是由于P2 X2和/或5受体，可能有P2 X4受体的贡献。我们的结论是，炎症诱导SGCs对ATP的敏感性大幅增加，这涉及从P2 Y到P2 X受体的转换。我们认为，SGCs对ATP的敏感性在损伤后增加了100倍以上，这可能有助于慢性疼痛状态。(C)2011爱思唯尔有限公司保留所有权利。
Satellite glial cells (SGCs) in sensory ganglia are altered structurally and biochemically as a result of nerve injury. Whereas there is ample evidence that P2 purinergic receptors in central glial cells are altered after injury, there is very little information on similar changes in SGCs, although it is well established that SGCs are endowed with P2 receptors. Using calcium imaging, we characterized changes in P2 receptors in SGCs from mouse trigeminal ganglia in short-term cultures. Seven days after the induction of submandibular inflammation with complete Freund's adjuvant, there was a marked increase in the sensitivity of SGCs to ATP, with the threshold of activation decreasing from 5 mu M to 10 nM. A similar observation was made in the intact trigeminal ganglion after infra-orbital nerve axotomy. Using pharmacological tools, we investigated the receptor mechanisms underlying these changes in cultured SGCs. We found that in control tissues response to ATP was mediated by P2Y (metabotropic) receptors, whereas after inflammation the response was mediated predominantly by P2X (ionotropic) receptors. As the contribution of P2X1,3,6 receptors was excluded, and the sensitivity to a P2X7 agonist did not change after inflammation, it appears that after inflammation the responses to ATP are largely due to P2X2 and/or 5 receptors, with a possible contribution of P2X4 receptors. We conclude that inflammation induced a large increase in the sensitivity of SGCs to ATP, which involved a switch from P2Y to P2X receptors. We propose that the over 100-fold augmented sensitivity of SGCs to ATP after injury may contribute to chronic pain states. (C) 2011 Elsevier Ltd. All rights reserved.