Isothiocyanates from Wasabia japonica activate transient receptor potential ankyrin 1 channel.
Isothiocyanates from Wasabia japonica activate transient receptor potential ankyrin 1 channel.
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来自山葵的异硫氰酸盐激活瞬时受体电位锚蛋白 1 通道。
DOI：
10.1093/chemse/bjs065
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发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
Nagai M & Tominaga M.
中科院分区：
文献类型：
--
作者：
Uchida K;Miura Y;Nagai M & Tominaga M.
6-（甲基亚磺酰基）己基异硫氰酸酯（6-MSITC）和6-（甲硫基）己基异硫氰酸酯（6-MTITC）具有较低的辛辣性，并且负责山葵（Wasabia japonica[Miq] Matsumura）的新鲜风味。在这项研究中，我们发现，这两个异硫氰酸酯激活瞬时受体电位锚蛋白1（TRPA 1），和6-MSITC激活瞬时受体电位香草素1（TRPV 1），但没有其他瞬时受体电位通道在感觉神经元中表达。6-MSITC和6-MTITC均可诱导表达小鼠TRPA 1（mTRPA 1）的人胚肾293细胞内Ca 2+升高，通过Ca 2+成像测量。在全细胞膜片钳记录中，6-MSITC和6-MTITC剂量依赖性地激活mTRPA 1（6-MSITC的EC 50 = 147±26 µM，6-MTITC的EC 50 = 30±3 µM）和人TRPA 1（hTRPA 1; 6-MSITC的EC 50 = 39±4 µM，6-MTITC的EC 50 = 34±3 µM）。此外，TRPA 1 N-末端半胱氨酸，据报道是重要的通道激活亲电配体，参与6-MSITC和6-MTITC诱发的TRPA 1激活。这些异硫氰酸酯还激活了在小鼠背根神经节神经元中表达的内源性TRPA 1和足底注射10- 30 mM 6-MSITC诱发的小鼠疼痛相关行为。这些结果表明：1）6-MSITC和6-MTITC激活mTRPA 1和hTRPA 1; 2）6-MSITC激活mTRPV 1; 3）这些异硫氰酸酯的药理学功能可能来自TRPA 1激活。
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) and 6-(methylthio)hexyl isothiocyanate (6-MTITC) have low pungency and are responsible for the fresh flavor of wasabi (Wasabia japonica[Miq] Matsumura). In this study, we found that these two isothiocyanates activate transient receptor potential ankyrin 1 (TRPA1), and 6-MSITC activates transient receptor potential vanilloid 1 (TRPV1), but not other transient receptor potential channels expressed in sensory neurons. Both 6-MSITC and 6-MTITCinduced intracellular Ca2+increases in human embryonic kidney-derived 293 cells expressing mouse TRPA1 (mTRPA1) as measured by Ca2+imaging. In whole-cell patch-clamp recordings, 6-MSITC and 6-MTITC dose-dependently activated both mTRPA1 (EC50= 147±26 µM for 6-MSITC and 30±3 µM for 6-MTITC) and human TRPA1 (hTRPA1; EC50= 39±4 µM for 6-MSITC and 34±3 µM for 6-MTITC). In addition, TRPA1 N-terminal cysteines, which are reported to be important for channel activation by electrophilic ligands, were involved in 6-MSITC- and 6-MTITC-evoked TRPA1 activation. These isothiocyanates also activated endogenous TRPA1 expressed in mouse dorsal root ganglion neurons and intraplantar injection of 10–30mM 6-MSITC-evoked pain-related behaviors in mice. These results indicate the following: 1) 6-MSITC and 6-MTITC activate both mTRPA1 and hTRPA1; 2) 6-MSITC activates mTRPV1; and 3) the pharmacological functions of these isothiocyanates could be derived from TRPA1 activation.