Avenali Luca, Abate Fulas Oli, Sondermann Julia, Narayanan Pratibha, Gomez-Varela David, Schmidt Manuela
a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
Channels (Austin). 2017 Jan 2;11(1):11-19. doi: 10.1080/19336950.2016.1207025. Epub 2016 Jun 30.
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.
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，如瞬时受体电位（TRP）A1离子通道。TRPA1在脊椎动物伤害感受和不同疼痛状态中起着关键作用。此外，TRPA1通道受到广泛的调节——这些过程进而影响伤害性信号传导。在这里，我们表明神经肽Nocistatin在背根神经节（DRG）培养的感觉神经元中应用TRPA1激动剂芥子油（MO）后，会使依赖TRPA1的钙内流敏感化。有趣的是，TRPV1介导的细胞钙反应不受Nocistatin影响。此外，通过DRG培养物中的siRNA介导的敲低评估，Nocistatin诱导的TRPA1敏感化可能独立于Nocistatin结合伴侣4-硝基苯基磷酸酶结构域和非神经元SNAP25样蛋白同源物1（NIPSNAP1）。总之，我们发现了Nocistatin对TRPA1的敏感化作用，这可能代表了Nocistatin调节疼痛的一种新机制。
