Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies
Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies
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香芹酚以不同的效力抑制非洲爪蟾卵母细胞中表达的神经元电压门控钠通道 Nav1.2、Nav1.6、Nav1.3、Nav1.7 和 Nav1.8
DOI：
10.1016/j.jphs.2019.12.009
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发表时间：
2020
影响因子：
3.5
通讯作者：
Minami Kouichiro
中科院分区：
文献类型：
--
作者：
Horishita Takafumi;Ogata Yuichi;Horishita Reiko;Fukui Ryo;Moriwaki Kuniaki;Ueno Susumu;Yanagihara Nobuyuki;Uezono Yasuhito;Sudo Yuka;Minami Kouichiro
香芹酚是许多芳香植物精油中主要的单萜化合物。几项动物实验显示了香芹酚的镇痛作用，这表明香芹酚有可能成为治疗难治性疼痛的新药。电压门控钠通道（Nav）被认为在炎症性和神经性疼痛的发展中起着至关重要的作用，但关于香芹酚的镇痛机制是否涉及Nav的信息有限。我们使用全细胞、双电极、电压钳技术检测了芹酚对表达Nav1.2、Nav1.3、Nav1.6、Nav1.7和Nav1.8 α亚基的异种卵母细胞钠电流的影响。Carvacrol剂量依赖性地抑制钠电流，其保持电位可诱导半最大电流。对Nav1.2、Nav1.3、Nav1.6、Nav1.7和Nav1.8的半极大抑制浓度分别为233、526、215、367和824 μmol/L，表明香芹酚对Nav1.2和Nav1.6的抑制作用强于Nav1.3、Nav1.7和Nav1.8。门控分析显示，在卡伐克罗处理后，所有5个α亚基的激活曲线发生去极化移动，失活曲线发生超极化移动。此外，香芹酚对所有5个α nav亚基都表现出使用依赖性阻滞。这些发现为更好地理解与香芹酚镇痛作用相关的机制提供了依据。
Carvacrol is the predominant monoterpene in essential oils from many aromatic plants. Several animal studies showing analgesic effects of carvacrol indicate potential of carvacrol as a new medication for patients with refractory pain. Voltage-gated sodium channels (Nav) are thought to have crucial roles in the development of inflammatory and neuropathic pain, but there is limited information about whether the analgesic mechanism of carvacrol involves Nav. We used whole-cell, two-electrode, voltage-clamp techniques to examine the effects of carvacrol on sodium currents inXenopusoocytes expressing α subunits of Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8. Carvacrol dose-dependently suppressed sodium currents at a holding potential that induced half-maximal current. The half-maximal inhibitory concentration values for Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 were 233, 526, 215, 367, and 824 μmol/L, respectively, indicating that carvacrol had more potent inhibitory effects towards Nav1.2 and Nav1.6 than Nav1.3, Nav1.7, and Nav1.8. Gating analysis showed a depolarizing shift of the activation curve and a hyperpolarizing shift of the inactivation curve in all five α subunits following carvacrol treatment. Furthermore, carvacrol exhibits a use-dependent block for all five α Navsubunits. These findings provide a better understanding of the mechanisms associated with the analgesic effect of carvacrol.