Potentiation of TRPV3 channel function by unsaturated fatty acids
Potentiation of TRPV3 channel function by unsaturated fatty acids
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DOI：
10.1002/jcp.20648
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发表时间：
2006-07-01
影响因子：
5.6
通讯作者：
Zhu, Michael X.
中科院分区：
文献类型：
--
作者：
Hu, Hong-Zhen;Xiao, Rui;Zhu, Michael X.
瞬时受体电位香草酸（TRPV）通道是多种环境因素（包括温度、pH和压力）的多模态检测器。炎症介质通过多种信号通路增强TRPV功能。花生四烯酸（AA）代谢的脂氧合酶和环氧合酶产物已被证明分别直接激活TRPV 1和TRPV 4。TRPV 3是一种热敏通道，其中间温度阈值为31-39 ℃。我们以前已经表明，TRPV 3被2-氨基乙氧基二苯基硼酸酯（2APB）激活。在这里，我们表明，AA和其他不饱和脂肪酸直接增强2APB诱导的反应，TRPV 3在HEK 293细胞，非洲爪蟾卵母细胞和小鼠角质形成细胞中表达。在细胞内Ca 2+测量、全细胞和双电极电压钳研究以及切除的由内而外和由外而外的斑块的单通道记录中观察到AA诱导的增强。脂肪酸诱导的增强作用不被蛋白激酶C的抑制剂阻断，因此不同于激酶诱导的增强作用。增强作用不需要AA代谢，而是通过AA的非代谢类似物来模拟。这些结果表明，一种新的机制，调节TRPV 3的炎症反应，这不同于TRPV 1和TRPV 4，并涉及直接作用的游离脂肪酸的通道。
Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31-39 degrees C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel.