GSK205 is a highly selective antagonist of the TRPV4 ion channel (IC50 = 4.19μM) [1]. GSK205 inhibits TRPV4 channel-mediated Ca²⁺ influx, thereby blocking activation signals triggered by mechanical stress, osmotic pressure changes, temperature, and chemical stimuli [2]. GSK205 is primarily used to study metabolic diseases, mechanical degenerative injury, and the mechanisms of inflammation and pain [3-4].
In 16HBE cells, after treatment with GSK205 (10μM; 1h), NLRP3 protein levels decreased, cleavage caspase-1 and GSDMD-N, and pro-caspase-1 and total GSDMD levels increased [5]. In HAEC cells, GSK205 (20μM; 2h) treatment induces inflammatory gene expression and NF-κB signaling [6].
In C57BL/6 mice, GSK205 (100μM; smear; single) effectively inhibits scratching behavior induced by histaminergic stimuli such as histamine, compound 48/80, or ET-1 [7]. In C57BL/6 mice, treated with GSK205 (1mM, 5mM; smear; single) showed reduced UVB-induced tissue damage from sunburn [8].
References:
[1]. Ye L, Kleiner S, Wu J, et al. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis[J]. Cell, 2012, 151(1): 96-110.
[2]. Tranter J D, Kumar A, Nair V K, et al. Mechanosensing in metabolism[J]. Comprehensive Physiology, 2024, 14(1): 5269-5290.
[3]. Fu S, Meng H, Inamdar S, et al. Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1β mediated articular cartilage matrix destruction[J]. Osteoarthritis and cartilage, 2021, 29(1): 89-99.
[4]. Thompson C, Knight M, Gupta H, et al. Activation of TRPV4 by mechanical, osmotic or pharmaceutical stimulation is anti-inflammatory blocking IL-1β mediated articular cartilage matrix destruction[J]. Osteoarthritis and Cartilage, 2020.
[5]. Rao Y, Gai X, Xiong J, et al. Transient receptor potential cation channel subfamily V member 4 mediates pyroptosis in chronic obstructive pulmonary disease[J]. Frontiers in Physiology, 2021, 12: 783891.
[6]. Hong S G, Ashby J W, Kennelly J P, et al. Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation[J]. The Journal of Clinical Investigation, 2024, 134(13).
[7]. Chen Y, Fang Q, Wang Z, et al. Transient receptor potential vanilloid 4 ion channel functions as a pruriceptor in epidermal keratinocytes to evoke histaminergic itch[J]. Journal of Biological Chemistry, 2016, 291(19): 10252-10262.
[8]. Moore C, Cevikbas F, Pasolli H A, et al. UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling[J]. Proceedings of the National Academy of Sciences, 2013, 110(34): E3225-E3234.
GSK205是TRPV4离子通道的高选择性拮抗剂（IC50 = 4.19μM） [1]。GSK205抑制TRPV4通道介导的Ca²⁺内流，从而阻断由机械应力、渗透压变化、温度和化学刺激触发的激活信号 [2]。GSK205主要用于研究代谢性疾病、机械退行性损伤以及炎症和疼痛的机制 [3-4]。
在16HBE细胞中，经GSK205（10μM；1h）处理后，NLRP3蛋白水平降低，caspase-1和GSDMD-N的裂解水平升高，pro-caspase-1和总GSDMD的水平升高 [5]。在HAEC细胞中，GSK205（20μM；2h）处理可诱导炎症基因表达和NF-κB信号传导 [6]。
在C57BL/6小鼠中，GSK205（100μM；涂抹；单次）有效抑制了histamine、化合物48/80或ET-1等组胺能刺激引起的抓挠行为 [7]。在C57BL/6小鼠中，用GSK205（1mM，5mM；涂抹；单次）治疗可减轻UVB引起的晒伤组织损伤 [8]。