Borneol Is a TRPM8 Agonist that Increases Ocular Surface Wetness.
Borneol Is a TRPM8 Agonist that Increases Ocular Surface Wetness.
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冰片是一种 TRPM8 激动剂，可增加眼表湿度
DOI：
10.1371/journal.pone.0158868
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zou F
中科院分区：
文献类型：
--
作者：
Chen GL;Lei M;Zhou LP;Zeng B;Zou F
冰片是我国眼用制剂中广泛使用的一种化合物。人们对它在治疗眼疾中的确切作用知之甚少。在这里，我们报告，瞬时受体电位melastatin 8（TRPM 8）通道是一个药理学的目标，并介导其治疗作用的眼睛。Ca 2+测定和电生理记录显示，TRPM 8通道的激活呈温度和剂量依赖性，这与已确定的TRPM 8激动剂薄荷醇的作用相似，但不如薄荷醇有效。冰片在25°C下显著增加豚鼠的泪液分泌，但不引起伤害性反应，但在35°C下不能诱导泪液分泌。相比之下，薄荷醇在25 ° C和35°C下均诱发流泪反应。TRPM 8通道阻断剂N-（3-氨基丙基）-2-[（3-甲基苯基）甲氧基]-N-（2-噻吩基甲基）苯甲酰胺盐酸盐（AMTB）和N-（4-叔丁基苯基）-4-（3-氯吡啶-2-基）哌嗪-1-甲酰胺（BCTC）可消除β-内酰胺和薄荷醇诱导的泪液分泌。微摩尔浓度的冰片不影响人角膜上皮细胞的活力。我们的结论是，ESTA可以激活冷敏感TRPM 8通道，并适度增加眼表湿润，这表明它是一种活性化合物的眼用制剂，特别是在治疗干眼综合征有用。
Borneol is a compound widely used in ophthalmic preparations in China. Little is known about its exact role in treating eye diseases. Here we report that transient receptor potential melastatin 8 (TRPM8) channel is a pharmacological target of borneol and mediates its therapeutic effect in the eyes. Ca2+ measurement and electrophysiological recordings revealed that borneol activated TRPM8 channel in a temperature- and dose-dependent manner, which was similar to but less effective than the action of menthol, an established TRPM8 agonist. Borneol significantly increased tear production in guinea pigs without evoking nociceptive responses at 25°C, but failed to induce tear secretion at 35°C. In contrast, menthol evoked tearing response at both 25 and 35°C. TRPM8 channel blockers N-(3-Aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)benzamide hydrochloride (AMTB) and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC) abolished borneol- and menthol-induced tear secretion. Borneol at micromolar concentrations did not affect the viability of human corneal epithelial cells. We conclude that borneol can activate the cold-sensing TRPM8 channel and modestly increase ocular surface wetness, which suggests it is an active compound in ophthalmic preparations and particularly useful in treating dry eye syndrome.