Mechanism of TRPA1 Activation

TRPA1 激活机制

• 批准号: 7156375
• 负责人: LINDSEY J MACPHERSON
• 金额: $ 3.08万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-16 至 2007-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156375
• 关键词: antioxidants; burns; cysteine; ions; mutant; neurons; pain; proteins; sensation; temperature

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.

描述（由申请人提供）：本提案的总体目标是有助于理解热感觉的机制。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，但人们对身体如何感知温度知之甚少。最近，非选择性阳离子通道的TRP家族成员已被证明在不同的温度范围内被激活。许多这些“热trp”也能够对天然化合物做出反应，这些化合物通过被称为化学反应的感觉产生燃烧、冷却或刺痛的辛辣感。TRPA1是一种有毒的冷感应通道，在支配口腔和舌头的痛觉神经元中表达，也能被刺激性化合物激活。肉桂醛、异硫氰酸烯丙酯和大蒜素激活TRPA1，产生肉桂红辣椒、山葵和生大蒜特有的灼烧感和刺痛感。在这篇论文中，我将研究TRPA1在寒冷和刺激性化学刺激下激活的分子机制。