2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3
2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3
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DOI：
10.1074/jbc.m404164200
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发表时间：
2004-08-20
影响因子：
4.8
通讯作者：
Zhu, MX
中科院分区：
文献类型：
--
作者：
Hu, HZ;Gu, QH;Zhu, MX
瞬时受体电位(Trp)超家族包含大量编码阳离子通透通道的蛋白质，这些蛋白质又分为TRPC(典范)、TRPM(Melastatin)和TRPV(香草素)亚家族。在6个TRPV成员中，TRPV1、TRPV2、TRPV3和TRPV4形成热激活的阳离子通道，具有从伤害性感受到渗透压调节的多种功能。尽管TRPV1和TRPV4的化学激活剂有很好的文献记载，但TRPV2和TRPV3的化学激活剂缺乏。在这里，我们发现在没有其他刺激的情况下，2-氨基乙氧基二苯硼酸酯(2APB)可以激活HEK293细胞中TRPV1、TRPV2和TRPV3的表达，但不激活TRPV4、TRPV5和TRPV6的表达。相反，2APB分别抑制1-油基-2-乙酰甘油和薄荷醇引起的TRPC6和TRPM8的活性。此外，低水平的2APB强烈增强辣椒素、质子和加热对非洲爪哇卵母细胞TRPV1和TRPV3表达的影响。在背根神经节神经元，2APB和辣椒素或2APB和酸可引起超加刺激。我们的数据表明，TRPV1、TRPV2和TRPV3存在一个共同的激活机制，可以作为疼痛管理和治疗由超敏和温度调节失调引起的疾病的治疗靶点。
The transient receptor potential (TRP) superfamily contains a large number of proteins encoding cation permeable channels that are further divided into TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) subfamilies. Among the six TRPV members, TRPV1, TRPV2, TRPV3, and TRPV4 form heat-activated cation channels, which serve diverse functions ranging from nociception to osmolality regulation. Although chemical activators for TRPV1 and TRPV4 are well documented, those for TRPV2 and TRPV3 are lacking. Here we show that in the absence of other stimuli, 2-aminoethoxydiphenyl borate (2APB) activates TRPV1, TRPV2, and TRPV3, but not TRPV4, TRPV5, and TRPV6 expressed in HEK293 cells. In contrast, 2APB inhibits the activity of TRPC6 and TRPM8 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively. In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes. In dorsal root ganglia neurons, supra-additive stimulations were evoked by 2APB and capsaicin or 2APB and acid. Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation.