• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Open Drug Discovery Journal >Therapeutic Potential of TRPM8 Modulators
【24h】

Therapeutic Potential of TRPM8 Modulators

机译：TRPM8调节剂的治疗潜力

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The perception of temperature is a key tenet of sensory physiology and is critical in not only acute responses tochanges in our environment, but also fundamental in regulating homeostatic mechanisms like core body temperature [1].The somatosensory system is able to detect subtle changes in ambient temperature due to the coordinated efforts ofthermosensory neurons which express temperature-sensitive members of the TRP channel family [2]. Remarkably, therange of temperatures that these channels respond to covers the entire perceived temperature spectrum, from warm topainfully hot, from pleasingly cool to excruciatingly cold. Moreover, many of these channels are receptors for ligands thatelicit distinct psychophysical sensations, such as the heat associated with capsaicin and the cold felt with menthol [2]. Thelatter of these was influential in the discovery of the first TRP channel shown to be responsive to temperatures in the coldrange (<30°C), TRPM8, a member of the melastatin TRP channel subfamily [3, 4]. In vitro, the channel is a receptor for anumber of compounds which evoke the psychophysical sensation of cold (such as menthol and icilin), and is activated bytemperatures that range from innocuous cool (26-15°C) to noxious cold (<15°C). Recent genetic evidence shows thatTRPM8 is the predominant mammalian cold sensor and is involved in most, if not all, aspects of cold thermal transduction[5-8]. These studies demonstrated that TRPM8 mediates transduction of innocuous cool and noxious cold,hypersensitivity to cold caused by inflammation or nerve injury, and provides the analgesic effect produced by cold orchemical cooling compounds. This review highlights these findings and suggests some potential uses of both TRPM8antagonists and agonists in the treatment of pain.
机译：对温度的感知是感觉生理学的一个关键原则，不仅对于对环境变化的急性反应至关重要，而且对于调节诸如核心体温的稳态机制也至关重要[1]。体感系统能够检测周围环境的细微变化。温度是由于表达TRP通道家族的温度敏感成员的热感觉神经元的协同作用引起的[2]。值得注意的是，这些通道响应的温度范围涵盖了整个感知的温度范围，从温暖到极热，从令人愉悦的凉到极酷的寒冷。此外，这些通道中的许多通道都是配体的受体，这些配体会引起不同的心理物理感觉，例如与辣椒素相关的热量和与薄荷醇相关的冷感[2]。这些因素对发现第一个TRP通道具有影响力，该通道显示出对寒冷范围（<30°C）的温度有响应，TRPM8是褪黑素TRP通道亚家族的成员[3，4]。在体外，该通道是许多化合物的受体，这些化合物会引起寒冷的心理物理感觉（例如薄荷醇和艾奇林），并在从无害凉爽（26-15°C）到有毒凉爽（<15°C）的温度范围内被激活。 C）。最近的遗传证据表明，TRPM8是哺乳动物的主要感温传感器，它参与了冷热传导的大部分（如果不是全部的话）[5-8]。这些研究表明TRPM8介导了无害的凉性和有害性冷，炎症或神经损伤引起的对感冒的超敏性的转导，并提供了由冷的或化学的凉爽化合物产生的镇痛作用。这篇综述强调了这些发现，并提出了TRPM8拮抗剂和激动剂在治疗疼痛中的某些潜在用途。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号