Involvement of nociceptive transient receptor potential channels in repellent action of pulegone
Involvement of nociceptive transient receptor potential channels in repellent action of pulegone
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DOI：
10.1016/j.bcp.2018.02.032
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发表时间：
2018-05-01
影响因子：
5.8
通讯作者：
Ohta, Toshio
中科院分区：
文献类型：
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作者：
Majikina, Azusa;Takahashi, Kenji;Ohta, Toshio
胡薄荷酮是一种鸟类驱避剂，用于预防鸟类造成的经济损失。化学驱避剂经常引起不愉快的感觉和感官刺激，导致在某些情况下避免。人们认识到一些表达感觉神经元的TRP通道与伤害感受有关。本研究利用分离的鸡感觉神经元和异源表达系统研究胡薄荷酮驱避作用的分子机制。胡薄荷酮可增加鸡感觉神经元胞内Ca ~（2+）浓度。有两种类型的神经元表现出不同的敏感性胡薄荷酮。一个在低浓度下对它有反应，另一个在高浓度下有反应。药理学分析表明，前者主要由TRP melastatin 8（TRPM 8）介导，后者由TRP锚蛋白1（TRPA 1）和TRPM 8介导。胡薄荷酮激活这两个通道也确定使用异源表达系统。在高浓度下，胡薄荷酮抑制鸡TRPM 8，但不是鸡TRPA 1。鸡足底注射胡薄荷酮引起疼痛相关行为，TRPA 1拮抗剂可减弱疼痛相关行为。这些结果表明，胡薄荷酮在高浓度下对鸡感觉神经元TRPM 8和TRPA 1通道都有刺激作用，对前者有抑制作用，但对后者无抑制作用。总之，这些数据表明，胡薄荷酮在鸟类物种中的驱避作用的分子靶标是伤害性TRPA 1。
Pulegone, one of avian repellents, is used to prevent the economic loss caused by birds. Chemical repellents often evoke unpleasant sensations and sensory irritation resulting in avoidance under some circumstances. It is recognized that some TRP channels expressing sensory neurons are related to nociception. Here we determined the molecular mechanisms of the repellent action of pulegone using isolated chicken sensory neurons and heterologous expression system. Pulegone increased the intracellular Ca2+ concentration ([Ca2+];) in chicken sensory neurons. There were two types of neurons exhibiting different sensitivity to pulegone. One was responded to it at low concentrations and the other at high concentrations. Pharmacological analyses revealed that the former was predominantly mediated by TRP melastatin 8 (TRPM8), and the latter by both TRP ankyrin 1 (TRPA1) and TRPM8. An activation of both channels by pulegone was also determined using heterologously expression system. At high concentrations, pulegone suppressed chicken TRPM8 but not chicken TRPA1. The intraplantar injection of pulegone in chicks caused pain-related behaviors that were attenuated by TRPA1 antagonist. These results indicate that pulegone stimulates both TRPM8 and TRPA1 channel in chicken sensory neurons and suppresses the former but not the latter at high concentrations. Together, these data suggest that the molecular target for the repellent action of pulegone in avian species is nociceptive TRPA1.