Mao Xiao-Li, Chen Yi-Xuan, Yu Huan, Yang Quan-Wei
Department of Pharmacy, Wuhan First Hospital, Wuhan, China.
Department of Pharmacy, Wuhan First Hospital, Wuhan, China.
Neurosci Lett. 2023 Apr 23;803:137192. doi: 10.1016/j.neulet.2023.137192. Epub 2023 Mar 15.
Eugenol is widely used as an analgesic in the dental treatment. The underlying mechanisms may involve its modulation of various ion channels. Acid-sensing ion channels (ASICs) are pH sensors and expressed in trigeminal ganglion (TG) neurons. In the present study, we found that eugenol concentration-dependently inhibited ASIC currents in TG neurons with an IC of 98.8 ± 7.4 μM. Eugenol decreased the maximum response to acidic pH and did not alter pH in the concentration-response curve of acidic pH, suggesting a noncompetitive inhibition of ASICs by eugenol. G-proteins were not involved in eugenol-induced inhibition, since pre-application of eugenol also decreased ASIC currents in the presence of the G-protein blocker GDP-β-S. In addition, eugenol also partly inhibited ASIC3 currents in Chinese hamster ovary cells transfected with ASIC3. In conclusion, eugenol partly inhibited ASIC currents in TG neurons in a concentration-dependent, non-competitive and G-protein independent manner. These results suggested that the ASICs could be a molecular target for eugenol in TG neurons, which contributed to its analgesic effect.
丁香酚在牙科治疗中被广泛用作镇痛药。其潜在机制可能涉及其对各种离子通道的调节作用。酸敏感离子通道（ASICs）是pH传感器，在三叉神经节（TG）神经元中表达。在本研究中，我们发现丁香酚浓度依赖性地抑制TG神经元中的ASIC电流，其半数抑制浓度为98.8±7.4μM。丁香酚降低了对酸性pH的最大反应，并且在酸性pH的浓度-反应曲线中不改变pH，表明丁香酚对ASICs具有非竞争性抑制作用。G蛋白不参与丁香酚诱导的抑制作用，因为在存在G蛋白阻断剂GDP-β-S的情况下预先应用丁香酚也会降低ASIC电流。此外，丁香酚还部分抑制了转染了ASIC3的中国仓鼠卵巢细胞中的ASIC3电流。总之，丁香酚以浓度依赖性、非竞争性和G蛋白非依赖性方式部分抑制TG神经元中的ASIC电流。这些结果表明，ASICs可能是丁香酚在TG神经元中的分子靶点，这有助于其镇痛作用。
