Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-1094, Japan.
J Pharmacol Exp Ther. 2013 Feb;344(2):459-66. doi: 10.1124/jpet.112.200063. Epub 2012 Dec 5.
Surfactants, an important component of cleansers, often cause itch in humans. Topical application of sodium laurate and N-lauroylsarcosine sodium salt to the skin of mice immediately (for 1-1.5 hours) increased scratching, and the former increased scratching again between 2 and 3 hours after application. Thus, we examined the mechanisms of sodium laurate-induced delayed scratching. Sodium laurate (0.1%-10%) increased delayed scratching and skin surface pH in a concentration-dependent manner. N-lauroylsarcosine sodium salt had no effect on these parameters, and sodium hydroxide solution did not increase delayed scratching. Sodium laurate-induced delayed scratching was markedly inhibited by the H(1) histamine receptor antagonist terfenadine, but it was not affected by mast cell deficiency. Sodium laurate application had no effect on the number of total and degranulated mast cells, and did not induce plasma extravasation or the infiltration of inflammatory cells in the skin. Sodium laurate application increased the histamine content of the epidermis, but not that of the dermis, in normal and mast cell-deficient mice. Sodium laurate application increased the ratio of 53-kDa l-histidine decarboxylase (HDC, a key enzyme for histamine production) to 74-kDa HDC in the mouse epidermis and in a human keratinocyte culture. Sodium laurate increased histamine in the human keratinocyte culture, without affecting cell viability. The present results suggest that sodium laurate induced delayed scratching at an alkaline pH through the increased production of histamine in keratinocytes, which may be due to enhanced processing of 74-kDa to 53-kDa HDC.
表面活性剂是清洁剂的重要组成部分，常引起人类瘙痒。将月桂酸钠和 N-月桂酰肌氨酸钠盐涂于小鼠皮肤，可立即（1-1.5 小时）增加搔抓，且前者在涂药后 2-3 小时再次增加搔抓。因此，我们研究了月桂酸钠引起的迟发性搔抓的机制。月桂酸钠（0.1%-10%）以浓度依赖方式增加迟发性搔抓和皮肤表面 pH。N-月桂酰肌氨酸钠盐对这些参数无影响，且氢氧化钠溶液不增加迟发性搔抓。H1 组胺受体拮抗剂特非那定明显抑制月桂酸钠引起的迟发性搔抓，但肥大细胞缺乏不影响其作用。月桂酸钠应用对总肥大细胞和脱颗粒肥大细胞的数量无影响，且不引起皮肤内血浆渗出或炎症细胞浸润。月桂酸钠应用增加正常和肥大细胞缺乏小鼠表皮而非真皮的组胺含量。月桂酸钠应用增加了小鼠表皮和人角质形成细胞培养物中 53-kDa l-组氨酸脱羧酶（HDC，组胺产生的关键酶）与 74-kDa HDC 的比值。月桂酸钠增加了人角质形成细胞培养物中的组胺，而不影响细胞活力。本结果提示，月桂酸钠在碱性 pH 下通过增加角质形成细胞中组胺的产生引起迟发性搔抓，这可能是由于增强了 74-kDa 向 53-kDa HDC 的加工。
