Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons
Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons
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DOI：
10.1080/19336950.2016.1207025
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发表时间：
2017-01-01
期刊：
影响因子：
3.3
通讯作者：
Schmidt, Manuela
中科院分区：
文献类型：
--
作者：
Avenali, Luca;Fulas, Oli Abate;Schmidt, Manuela
感觉神经元检测潜在有害刺激的能力依赖于专门的分子信号检测器，例如瞬时受体电位（TRP）A1离子通道。TRPA 1与脊椎动物的伤害感受和不同的疼痛状态密切相关。此外，TRPA 1通道受到广泛的调制和调节-从而影响伤害性信号传导的过程。在这里，我们表明，神经肽Nocistatin增敏TRPA 1依赖的钙内流后，应用TRPA 1激动剂芥子油（MO）培养的感觉神经元的背根神经节（DRG）。有趣的是，TRPV 1介导的细胞钙反应不受Nocistatin的影响。此外，如通过DRG培养物中siRNA介导的敲低所评估的，Nocistatin诱导的TRPA 1致敏可能不依赖于Nocistatin结合配偶体4-硝基苯磷酸酶结构域和非神经元SNAP 25样蛋白同系物1（NIPSNAP 1）。总之，我们揭示了TRPA 1通过Nocistatin的敏化，这可能代表了Nocistatin如何调节疼痛的新机制。
The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling. Here we show that the neuropeptide Nocistatin sensitizes TRPA1-dependent calcium influx upon application of the TRPA1 agonist mustard oil (MO) in cultured sensory neurons of dorsal root ganglia (DRG). Interestingly, TRPV1-mediated cellular calcium responses are unaffected by Nocistatin. Furthermore, Nocistatin-induced TRPA1-sensitization is likely independent of the Nocistatin binding partner 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) as assessed by siRNA-mediated knockdown in DRG cultures. In conclusion, we uncovered the sensitization of TRPA1 by Nocistatin, which may represent a novel mechanism how Nocistatin can modulate pain.