Partial Activation and Inhibition of TRPV1 Channels by Evodiamine and Rutaecarpine, Two Major Components of the Fruits of Evodia rutaecarpa.
Partial Activation and Inhibition of TRPV1 Channels by Evodiamine and Rutaecarpine, Two Major Components of the Fruits of Evodia rutaecarpa.
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DOI：
10.1021/acs.jnatprod.5b00599
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发表时间：
2016-05
影响因子：
5.1
通讯作者：
Shenglan Wang;Satoshi Yamamoto;Yoko Kogure;Wensheng Zhang;K. Noguchi;Yi Dai
中科院分区：
文献类型：
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作者：
Shenglan Wang;Satoshi Yamamoto;Yoko Kogure;Wensheng Zhang;K. Noguchi;Yi Dai
吴茱萸碱(1)和吴茱萸次碱(2)是吴茱萸的两个主要成分，长期以来一直被传统医学用于治疗多种疾病。利用表达瞬时受体电位香草素1(TRPV1)的HEK293细胞和膜片钳记录，研究了1和2对TRPV1通道的抑制作用。评估了这些化合物对辣椒素或质子激活的TRPV1活性的影响。结果表明，虽然1和2能激活TRPV1，但其最大反应分别比辣椒素低3.5倍或9倍，提示部分激动性。与辣椒素相比，1和辣椒素合用增加了辣椒素激活的TRPV1电流的半数有效浓度(EC50)，剂量-反应曲线右移，而1和质子合用不能抑制质子诱发的电流。此外，预先给药1，而不是2，可抑制辣椒素和质子诱发的TRPV1电流，这可能涉及通道脱敏。综上所述，1和2可能与辣椒素有相同的结合部位，并作为TRPV1的部分激动剂(拮抗剂)。吴茱萸碱(1)可使TRPV1脱敏或竞争性抑制TRPV1的活性，吴茱萸次碱(2)无此作用。
Evodiamine (1) and rutaecarpine (2) are the two major components of Evodia rutaecarpa, which has long been used in traditional medicine for the treatment of many diseases. Using transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells and patch-clamp recording, the inhibitory actions of 1 and 2 against TRPV1 channels were investigated. The effects of these compounds against capsaicin- or proton-activated TRPV1 activities were evaluated. The results showed that, although 1 and 2 can activate TRPV1, the maximum response was 3.5- or 9-fold lower than that of capsaicin, respectively, suggesting partial agonism. In comparison to capsaicin, coadministration of 1 and capsaicin increased the half-maximal effective concentration (EC50) of capsaicin-activated TRPV1 currents as shown by a right shift in the dose-response curve, whereas coadministration of 1 with protons failed to inhibit the proton-induced current. Moreover, preadministration of 1, but not 2, inhibited both capsaicin- and proton-induced TRPV1 currents, which might involve channel desensitization. Taken together, 1 and 2 may share the same binding site with capsaicin and act as partial agonists (antagonists) of TRPV1. Evodiamine (1), but not rutaecarpine (2), can desensitize or competitively inhibit the activity of TRPV1.