Centro de Investigación Príncipe Felipe, Valencia, Spain.
Adv Exp Med Biol. 2011;704:491-515. doi: 10.1007/978-94-007-0265-3_27.
The capsaicin receptor TRPV1 (Transient Receptor Potential, Vanilloid family member 1), the founding member of the heat-sensitive TRP ("thermo-TRP") channel family, plays a pivotal role in pain transduction. There is mounting evidence that TRPV1 regulation is complex and is manifest at many levels, from gene expression through post-translational modification and formation of receptor heteromers to subcellular compartmentalization and association with regulatory proteins. These mechanisms are believed to be involved both in disease-related changes in TRPV1 expression, and the long-lasting refractory state, referred to as "desensitization", that follows TRPV1 agonist treatment. The signaling cascades that regulate TRPV1 and related thermo-TRP channels are only beginning to be understood. Here we review our current knowledge in this rapidly changing field. We propose that the complex regulation of TRPV1 may be exploited for therapeutic purposes, with the ultimate goal being the development of novel, innovative agents that target TRPV1 in diseased, but not healthy, tissues. Such compounds are expected to be devoid of the side-effects (e.g. hyperthermia and impaired noxious heat sensation) that plague the clinical use of existing TRPV1 antagonists.
辣椒素受体 TRPV1（瞬时受体电位香草素家族成员 1）是热敏 TRP（“热 TRP”）通道家族的创始成员，在痛觉传递中发挥关键作用。越来越多的证据表明，TRPV1 的调节非常复杂，表现在多个层面上，从基因表达到翻译后修饰和受体异聚体的形成，再到细胞亚区室化和与调节蛋白的关联。这些机制被认为既参与了 TRPV1 表达的与疾病相关的变化，也参与了 TRPV1 激动剂治疗后出现的持久的难治状态，即“脱敏”。调节 TRPV1 和相关热敏 TRP 通道的信号级联反应才刚刚开始被理解。在这里，我们回顾了这一快速变化领域的现有知识。我们提出，TRPV1 的复杂调节可能被用于治疗目的，最终目标是开发新型创新药物，以在患病但健康组织中靶向 TRPV1。这些化合物有望避免现有 TRPV1 拮抗剂临床应用中存在的副作用（例如发热和有害热感觉受损）。
