Inoue Kazuhide
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University.
Yakugaku Zasshi. 2013;133(10):1035-9. doi: 10.1248/yakushi.13-00191.
A growing body of evidence indicates that extracellular nucleotides released or leaked from non-excitable cells as well as neurons play important roles in the regulation of neuronal and glial functions in the whole body through ATP receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the most abundant receptor families in living organisms. In the central nervous system, these receptors participate in synaptic transmission and in intercellular communications between neurons and glia. Glia cells are classified into astrocytes, oligodendrocytes and microglia. There are many reports on the role of ATP receptors (P2X4, P2X7, P2Y6 and P2Y12 receptors) expressed in spinal microglia. We have reported that several molecules presumably activate microglia in neuropathic pain after peripheral nerve injury. P2X4 receptors expressed in microglia in particular play a critical role in neuropathic pain signaling. The expression and activity of P2X4 receptors are up-regulated and enhanced predominantly in activated microglia in the spinal cord where damaged sensory fibers project. These findings provide novel targets for developing new medicines to treat neuropathic pain.
越来越多的证据表明，从非兴奋性细胞以及神经元释放或泄漏的细胞外核苷酸通过ATP受体在调节全身神经元和神经胶质细胞功能中发挥重要作用。ATP受体（离子型P2X和代谢型P2Y受体）是生物体内最丰富的受体家族。在中枢神经系统中，这些受体参与突触传递以及神经元与神经胶质细胞之间的细胞间通讯。神经胶质细胞分为星形胶质细胞、少突胶质细胞和小胶质细胞。关于脊髓小胶质细胞中表达的ATP受体（P2X4、P2X7、P2Y6和P2Y12受体）的作用有许多报道。我们已经报道，在周围神经损伤后，几种分子可能会激活神经性疼痛中的小胶质细胞。特别是小胶质细胞中表达的P2X4受体在神经性疼痛信号传导中起关键作用。P2X4受体的表达和活性在受损感觉纤维投射的脊髓中主要在活化的小胶质细胞中上调和增强。这些发现为开发治疗神经性疼痛的新药提供了新的靶点。
