Surfactant cocamide monoethanolamide causes eye irritation by activating nociceptor TRPV1 channels.
Surfactant cocamide monoethanolamide causes eye irritation by activating nociceptor TRPV1 channels.
复制标题
表面活性剂椰油酰胺单乙醇酰胺通过激活伤害感受器 TRPV1 通道引起眼睛刺激。
DOI：
10.1111/bph.15491
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Cao Zhengyu
中科院分区：
文献类型：
--
作者：
Zhao Fang;Wang Shuangyan;Li Yan;Wang Jin;Wang Yujing;Zhang Chunlei;Li Yong;Huang Longjiang;Yu Ye;Zheng Jie;Yu Boyang;Pessah Isaac N;Cao Zhengyu
背景和目的椰油酰胺单乙醇酰胺（CMEA）通常用作化妆品配方中的表面活性剂泡沫促进剂。当接触眼睛或其他敏感皮肤区域时，CMEA会产生刺痛和持久刺激。我们假设与TRPV 1通道的特定分子相互作用使CMEA引起眼刺激。实验方法使用兔和小鼠的擦眼试验评估眼刺激性。分别用钙离子成像和电流钳技术测定细胞内钙离子浓度和动作电位。采用电压钳、定点突变和分子模拟等方法鉴定TRPV 1通道上CMEA的结合口袋。Key ResultsCMEA诱导的眼刺激可通过选择性消融TRPV 1通道而得到改善。啮齿动物对CMEA的反应远强于兔。在三叉神经节神经元中，CMEA诱导Ca 2+内流和神经元兴奋性，TRPV 1通道抑制减轻了这种效应，而TRPV 1敲除神经元中则不存在这种效应。在表达TRPV 1通道的HEK-293细胞中，CMEA通过增加通道开放概率（EC 50 = 10.2 μM）增加全细胞电流，而不影响TRPV 2、TRPV 3、TRPV 4和TRPA 1通道活性。月桂酸单乙醇酰胺（LAMEA）是CMEA中最丰富的成分，是最有效和最有效的TRPV 1通道激活剂，与通道的辣椒素结合口袋结合。T550 I突变体的兔和人TRPV 1通道表现出低得多的敏感性LAMEA.Conclusions和ImplicationCMEA直接激活TRPV 1通道产生眼刺激。家兔是眼刺激性试验的标准动物，是评价与CMEA结构相关的人眼刺激性的不良模型。我们的研究确定了CMEA作为无刺激性表面活性剂的潜在替代品。
Background and PurposeCocamide monoethanolamide (CMEA) is commonly used as a surfactant‐foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits stinging and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 channels by which CMEA caused eye irritation.Experimental ApproachEye irritancy was evaluated using eye‐wiping tests in rabbits and mice. Intracellular Ca2+concentrations and action potentials were measured using Ca2+imaging and current clamp respectively. Voltage clamp, site‐direct mutagenesis and molecular modelling were used to identify binding pockets for CMEA on TRPV1 channels.Key ResultsCMEA‐induced eye irritation is ameliorated by selective ablation of TRPV1 channels.Rodents exhibit much stronger responses to CMEA than rabbits. In trigeminal ganglion neurons, CMEA induced Ca2+influx and neuronal excitability, effects mitigated by a TRPV1 channel inhibition and absent in TRPV1 knockout neurons. In HEK‐293 cells expressing TRPV1 channels, CMEA increased whole‐cell currents by increasing channel open probability (EC50= 10.2 μM), without affecting TRPV2, TRPV3, TRPV4, and TRPA1 channel activities. Lauric acid monoethanolamide (LAMEA), the most abundant constituent of CMEA, was the most efficacious and potent TRPV1 channel activator, binding to the capsaicin‐binding pocket of the channel. The T550I mutants of rabbit and human TRPV1 channels exhibit much lower sensitivity to LAMEA.Conclusions and ImplicationCMEA directly activates TRPV1 channels to produce eye irritation. Rabbits, the standard animal used for eye irritancy tests are poor models for evaluating human eye irritants structurally related to CMEA. Our study identifies potential alternatives to CMEA as non‐irritating surfactants.