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首页> 外文期刊>The European Journal of Neuroscience >Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain.
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Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain.

机译:A / J近交小鼠品系中P2X3受体依赖的感觉功能的下调。

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There is large variability in the various pain responses including those to tissue injury among inbred mouse strains. However, the determinant factors for the strain-specific differences remain unknown. The P2X3 sensory-specific ATP-gated channel has been implicated as a damage-sensing molecule that evokes a pain sensation by receiving endogenous ATP from injured tissue. In this study, to clarify the contribution of the sensory P2X3 signalling to strain-specific differences in tissue injury pain, we examined whether the P2X3-mediated in vivo and in vitro responses in dorsal root ganglion (DRG) neurons are changed in the A/J inbred mouse strain, which is known to be resistant to tissue injury pain caused by formalin. Here we found that A/J mice exhibited a low magnitude of nocifensive behaviour induced by the P2X agonist alpha,beta-methylene ATP (alpha beta meATP) into the hindpaw compared with C57BL/6 J mice. This behaviour was blocked by P2X3 antisense oligodeoxynucleotides. The low magnitude of the in vivo pain sensation could be observed similarly in the in vitro response; the increase in the intracellular Ca(2+) increase by alpha beta meATP in capsaicin-sensitive DRG neurons from A/J mice was significantly lower than that from C57BL/6 J mice. In A/J DRG neurons the P2X3 protein level was significantly lower compared with C57BL/6 J DRG neurons. The change in P2X3 protein was selective because P2X2 protein was expressed equally in both strains. The present study suggests that the downregulation of sensory P2X3 could be one of the molecular predispositions to low sensitivity to tissue injury pain in the A/J inbred mouse strain.
机译:在近交小鼠品系中,各种疼痛反应(包括对组织损伤的反应)存在很大差异。但是,菌株特异性差异的决定因素仍然未知。 P2X3感官特异的ATP门控通道被认为是一种损伤感应分子,通过从受伤的组织接受内源性ATP来引起疼痛感觉。在这项研究中,为弄清感觉P2X3信号传导对组织损伤疼痛中菌株特异性差异的贡献,我们检查了A / A中背根神经节(DRG)神经元中P2X3介导的体内和体外反应是否发生了改变J自交系小鼠品系,已知对福尔马林引起的组织损伤疼痛具有抵抗力。在这里,我们发现与C57BL / 6 J小鼠相比,A / J小鼠表现出由P2X激动剂α,β-亚甲基ATP(αβmeATP)诱导的后足低等价的伤害行为。 P2X3反义寡聚脱氧核苷酸阻止了这种行为。在体外反应中可以类似地观察到较低的体内疼痛感。辣椒素敏感的DRG神经元从A / J小鼠中通过alpha beta meATP的细胞内Ca(2+)的增加明显低于C57BL / 6 J小鼠。与C57BL / 6 J DRG神经元相比,A / J DRG神经元的P2X3蛋白水平明显降低。 P2X3蛋白的变化是选择性的,因为P2X2蛋白在两种菌株中均表达。本研究表明,感觉P2X3的下调可能是A / J自交系小鼠对组织损伤疼痛敏感性低的分子诱因之一。

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