用 TRP 通道感知冷热。

Sensing hot and cold with TRP channels.

机构信息

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Int J Hyperthermia. 2011;27(4):388-98. doi: 10.3109/02656736.2011.554337.

Abstract

The past decade has witnessed the cloning of a new family of ion channels that are responsive to temperature. Six of these transient receptor potential (TRP) channels are proposed to be involved in thermosensation and are located in sensory nerves and skin. The TRPV1, TRPV2, TRPV3, and TRPV4 channels have incompletely overlapping functions over a broad thermal range from warm to hot. Deletion of the individual TRPV1, TRPV3, and TRPV4 channels in mice has established their physiological role in thermosensation. In all cases thermosensation is not completely abolished - suggesting some functional redundancy among the channels. Notably, the TRPV2 channel is responsive to hot temperatures in heterologous systems, but its physiological relevance in vivo has not been established. Cool and cold temperatures are sensed by TRPM8 and TRPA1 family members. Currently, the pharmaceutical industry is developing agonists and antagonists for the various TRP channels. For instance, TRPV1 receptor agonists produce hypothermia, while antagonists induce hyperthermia. Recent investigations have found that different regions of the TRPV1 receptor are responsive to temperature, nociceptive stimuli, and various chemical agents. With this information, it has been possible to develop a TRPV1 compound that blocks responses to capsaicin and acid while leaving temperature sensitivity intact. These channels have important implications for hyperthermia research and may help to identify previously unexplored mechanisms in different tissues that are responsive to thermal stress.

摘要

过去十年见证了一类新的对温度敏感的离子通道的克隆。其中六个瞬时受体电位 (TRP) 通道被认为参与热感觉,位于感觉神经和皮肤中。 TRPV1、TRPV2、TRPV3 和 TRPV4 通道在从温暖到炎热的广泛温度范围内具有不完全重叠的功能。在小鼠中删除单个 TRPV1、TRPV3 和 TRPV4 通道已确立了它们在热感觉中的生理作用。在所有情况下,热感觉并未完全消除 - 表明通道之间存在一些功能冗余。值得注意的是,TRPV2 通道在异源系统中对热温度有反应,但在体内的生理相关性尚未确定。TRPM8 和 TRPA1 家族成员感知凉爽和寒冷的温度。目前,制药行业正在开发各种 TRP 通道的激动剂和拮抗剂。例如,TRPV1 受体激动剂会导致体温过低,而拮抗剂会引起体温过高。最近的研究发现,TRPV1 受体的不同区域对温度、伤害性刺激和各种化学物质有反应。有了这些信息,就有可能开发出一种 TRPV1 化合物,该化合物可阻断对辣椒素和酸的反应,同时保持温度敏感性。这些通道对高热研究具有重要意义,并可能有助于确定不同组织中以前未探索到的对热应激有反应的机制。

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