Choi Da-Som, Ji Yeounjung, Jang Yongwoo, Lee Wook-Joo, Shim Won-Sik
College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.
Gachon Institute of Pharmaceutical Sciences, Incheon 21936, Republic of Korea.
Biomol Ther (Seoul). 2020 Nov 1;28(6):569-575. doi: 10.4062/biomolther.2020.063.
Crotamiton is an anti-scabies drug, but it was recently found that crotamiton also suppresses non-scabietic itching in mice. However, the underlying mechanism is largely unclear. Therefore, aim of the study is to investigate mechanisms of the anti-pruritic effect of crotamiton for non-scabietic itching. Histamine and chloroquine are used as non-scabietic pruritogens. The effect of crotamiton was identified using fluorometric intracellular calcium assays in HEK293T cells and primary cultured dorsal root ganglion (DRG) neurons. Further effect was evaluated by scratching behavior tests. Crotamiton strongly inhibited histamine-induced calcium influx in HEK293T cells, expressing both histamine receptor 1 (H1R) and transient receptor potential vanilloid 1 (TRPV1), as a model of histamine-induced itching. Similarly, it also blocked chloroquine-induced calcium influx in HEK293T cells, expressing both Mas-related G-protein-coupled receptor A3 (MRGPRA3) and transient receptor potential A1 (TRPA1), as a model of histamine-independent itching. Furthermore, crotamiton also suppressed both histamine- and chloroquine-induced calcium influx in primary cultures of mouse DRG. Additionally, crotamiton strongly suppressed histamine- and chloroquine-induced scratching in mice. Overall, it was found that crotamiton has an anti-pruritic effect against non-scabietic itching by histamine and chloroquine. Therefore, crotamiton may be used as a general anti-pruritic agent, irrespective of the presence of scabies.
克罗米通是一种抗疥疮药物，但最近发现它也能抑制小鼠的非疥疮性瘙痒。然而，其潜在机制尚不清楚。因此，本研究的目的是探讨克罗米通对非疥疮性瘙痒的止痒作用机制。组胺和氯喹被用作非疥疮性致痒原。使用荧光细胞内钙测定法在HEK293T细胞和原代培养的背根神经节（DRG）神经元中确定克罗米通的作用。通过抓挠行为测试评估进一步的效果。作为组胺诱导瘙痒的模型，克罗米通强烈抑制组胺诱导的钙流入HEK293T细胞，该细胞同时表达组胺受体1（H1R）和瞬时受体电位香草酸亚型1（TRPV1）。同样，作为组胺非依赖性瘙痒的模型，它也阻断氯喹诱导的钙流入HEK293T细胞，该细胞同时表达Mas相关G蛋白偶联受体A3（MRGPRA3）和瞬时受体电位A1（TRPA1）。此外，克罗米通还抑制小鼠DRG原代培养物中组胺和氯喹诱导的钙流入。此外，克罗米通强烈抑制小鼠中组胺和氯喹诱导的抓挠。总体而言，发现克罗米通对组胺和氯喹引起的非疥疮性瘙痒具有止痒作用。因此，无论是否存在疥疮，克罗米通都可作为一种通用的止痒剂。
