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首页> 外文期刊>Glia >P2X(7) receptor stimulation in primary cultures of rat spinal microglia induces downregulation of the activity for glutamate transport
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P2X(7) receptor stimulation in primary cultures of rat spinal microglia induces downregulation of the activity for glutamate transport

机译：大鼠脊髓小胶质细胞原代培养中的P2X（7）受体刺激诱导谷氨酸转运活性的下调

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It has been shown that spinal microglia expressing certain types of glutamate transporters function in the modulation of neuropathogenesis. In this study, the effect of ATP, potentially able to mediate the communication between neurons and glial cells in the spinal cord on the transport of glutamate in cultured spinal microglia, was investigated. Both GLAST and GLT-1 were detected in the cells. Preincubation with ATP or 2'-3'-O-(4-benzoyl-benzoyl) ATP (BzATP), a selective agonist for the P2X(7) receptor, significantly blocked the uptake of glutamate. The effect of BzATP was reversed by pretreatment with brilliant blue G or oxidized ATP, each a selective antagonist for P2X(7). The inhibitory effect of P2X(7) receptor activation also occurred in the absence of extracellular Na+ or Ca2+, suggesting that the receptor regulates glutamate transport by a metabotropic pathway. Furthermore, pretreatment with inhibitors of mitogen-activated protein kinase kinase, or antioxidants, significantly reversed the inhibitory effect of BzATP on the uptake of glutamate. Incubation with BzATP led to a marked decrease in the V-max, but not the K-m, of glutamate transport. However, treatment with BzATP did not induce the trafficking of glutamate transporters. These results suggest that the activation of P2X(7) receptors in spinal microglia is important in the regulation of glutamate transport via activation of the extracellular signal-regulated kinase cascade and production of oxidants. (C) 2008 Wiley-Liss, Inc.
机译：已经表明，表达某些类型的谷氨酸转运蛋白的脊髓小胶质细胞在神经发病机理的调节中起作用。在这项研究中，研究了ATP可能介导脊髓神经元和神经胶质细胞之间的通讯对培养的脊髓小胶质细胞中谷氨酸转运的影响。在细胞中检测到了GLAST和GLT-1。与ATP或2'-3'-O-（4-苯甲酰基-苯甲酰基）ATP（BzATP）（P2X（7）受体的选择性激动剂）预先孵育，可显着阻止谷氨酸的吸收。通过用亮蓝G或氧化的ATP预处理可以逆转BzATP的作用，每种都是P2X的选择性拮抗剂（7）。 P2X（7）受体激活的抑制作用也发生在不存在细胞外Na +或Ca2 +的情况下，表明该受体通过代谢途径调节谷氨酸转运。此外，用促分裂原活化的蛋白激酶激酶的抑制剂或抗氧化剂进行的预处理显着逆转了BzATP对谷氨酸摄取的抑制作用。与BzATP一起孵育会导致谷氨酸转运的V-max显着降低，但K-m却没有显着降低。但是，用BzATP进行的治疗不会诱导谷氨酸转运蛋白的转运。这些结果表明，脊柱小胶质细胞中P2X（7）受体的激活通过激活细胞外信号调节激酶的级联反应和氧化剂的产生，在谷氨酸的转运中起着重要的作用。 （C）2008 Wiley-Liss，Inc.

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