Mechanism of TRPA1 Activation

描述(由申请人提供)：本提案的总体目标是促进对温度补偿基础机制的理解。对温度的感觉和基于这些感觉调节体温的能力是哺乳动物生物学的一个非常基本的要求。尽管这一过程具有基本的性质，但人们对人体如何感知温度知之甚少。最近，非选择性阳离子通道Trp家族的成员被证明在不同的温度范围内被激活。这些“热刺激反应蛋白”中的许多也能够对天然化合物产生反应，这些化合物通过一种称为化学合成的感觉产生灼热、降温或刺痛的刺激性。TRPA1是一种有毒的冷感觉通道，表达于支配口腔和舌头的痛觉神经元，也可以被刺激性化合物激活。肉桂醛、异硫氰酸烯丙酯和大蒜素能激活TRPA1，并产生肉桂红薯、山葵和生大蒜特有的灼烧感和刺痛感。在这个提案中，我将研究寒冷和刺激性化学刺激激活TRPA1‘S的分子机制。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to contribute to the understanding of the mechanisms that underlie thermosensation. The sensation of temperature and the ability to regulate body temperature based on those sensations is a very basic requirement of mammalian biology. Despite the basic nature of this process, little is known about exactly how the body can sense temperature. Recently, members of the TRP family of non-selective cation channels have been shown to be activated in response to different temperature ranges. Many of these "thermoTRPs" are also able to respond to natural compounds which produce a burning, cooling, or prickling pungency through the sensation known as chemesthesis. TRPA1, a noxious cold sensing channel expressed in the pain-sensing neurons innervating the mouth and tongue, is also able to be activated by pungent compounds. Cinnamaldehyde, allyl isothiocyanate, and allicin activate TRPA1 and produce the characteristic burning, prickling sensations of cinnamon red-hots, wasabi, and raw garlic. In this proposal, I will investigate the molecular mechanisms involved in TRPA1's activation by cold and pungent chemical stimuli.