Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Apartado 18, San Juan de Alicante, 03550 Spain.
Curr Pharm Biotechnol. 2011 Jan 1;12(1):54-67. doi: 10.2174/138920111793937916.
Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in a subpopulation of cold-sensitive sensory neurons, as well as in the male urogenital system. TRPM8 is markedly upregulated in prostate cancer and in other tumors such as breast adenocarcinoma and melanoma. Moreover, recent studies suggest the potential involvement of TRPM8 channels in the pathophysiology of cold nociception and cold allodynia. This has led to a strong interest in the pursuit of novel modulators of TRPM8 channels. This review highlights our current knowledge of TRPM8 pharmacology and modulation mechanisms, detailing structural features important for TRPM8 gating by different agonists, the mechanism of antagonism by different compounds and the potential relevance of TRPM8 for treatment of various pathological conditions.
瞬时受体电位 melastatin 8（TRPM8）是一种非选择性阳离子通道，可被低温和冷却剂激活。TRPM8 表达于冷敏感觉神经元亚群以及男性泌尿生殖系统中。TRPM8 在前列腺癌和其他肿瘤（如乳腺癌腺癌和黑色素瘤）中显著上调。此外，最近的研究表明 TRPM8 通道可能参与冷伤害感受和冷过敏的病理生理学。这导致了对 TRPM8 通道新型调节剂的强烈兴趣。这篇综述强调了我们目前对 TRPM8 药理学和调节机制的认识，详细介绍了不同激动剂对 TRPM8 门控作用的结构特征、不同化合物的拮抗机制以及 TRPM8 在治疗各种病理状况中的潜在相关性。
