A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic

A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic
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DOI:
10.1038/nn2056
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发表时间:
2008-03-01
影响因子:
25
通讯作者:
Rosenbaum, Tamara
Rosenbaum, Tamara
中科院分区:
医学1区
文献类型:
--
作者:
Salazar, Hector;Llorente, Itzel;Rosenbaum, Tamara

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阳离子通道的瞬时受体电位(TRP)家族的一些成员介导对刺激物质的感觉反应。尽管众所周知,TRPA 1通道被大蒜、洋葱、芥末和肉桂提取物中发现的辛辣化合物激活,但这些提取物对TRPV 1的激活仍然存在争议。在这里,我们确定TRPV 1被洋葱和大蒜的辛辣提取物以及这些制剂中的活性化合物大蒜素激活,并与TRPA 1一起参与该化合物诱导的疼痛相关行为。我们发现,在TRPV 1这些代理人的行动,通过共价修饰的半胱氨酸残基。与TRPA 1通道相反,位于TRPV 1 N-末端区域的单个半胱氨酸的修饰对于我们观察到的所有效应是必要的和足够的。我们的研究结果指出了TRP通道激活的保守机制,这为伤害性刺激检测的分子基础提供了新的见解。
Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.