Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany.
Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Münster, Germany,
Cell Physiol Biochem. 2021 May 28;55(S3):108-130. doi: 10.33594/000000358.
Transient receptor potential vanilloid (TRPV) channels are part of the TRP channel superfamily and named after the first identified member TRPV1, that is sensitive to the vanillylamide capsaicin. Their overall structure is similar to the structure of voltage gated potassium channels (K) built up as homotetramers from subunits with six transmembrane helices (S1-S6). Six TRPV channel subtypes (TRPV1-6) are known, that can be subdivided into the thermoTRPV (TRPV1-4) and the Ca-selective TRPV channels (TRPV5, TRPV6). Contrary to K channels, TRPV channels are not primary voltage gated. All six channels have distinct properties and react to several endogenous ligands as well as different gating stimuli such as heat, pH, mechanical stress, or osmotic changes. Their physiological functions are highly diverse and subtype as well as tissue specific. In many tissues they serve as sensors for different pain stimuli (heat, pressure, pH) and contribute to the homeostasis of electrolytes, the maintenance of barrier functions and the development of macrophages. Due to their fundamental role in manifold physiological and pathophysiological processes, TRPV channels are promising targets for drug development. However, drugs targeting specific TRPV channels, that are suitable for drug therapy, are rare. Moreover, selective and potent compounds for further research at TRPV channels are often lacking. In this review different aspects of the structure, the different gating stimuli, the expression pattern, the physiological and pathophysiological roles as well as the modulating mechanisms of synthetic, natural and endogenous ligands are summarized.
瞬时受体电位香草酸 (TRPV) 通道是 TRP 通道超家族的一部分，以第一个被鉴定的成员 TRPV1 命名，该通道对香草酰胺辣椒素敏感。它们的整体结构类似于由六个跨膜螺旋 (S1-S6) 组成的同源四聚体构成的电压门控钾通道 (K) 的结构。目前已知有六种 TRPV 通道亚型 (TRPV1-6)，可分为热 TRPV (TRPV1-4) 和 Ca 选择性 TRPV 通道 (TRPV5、TRPV6)。与 K 通道不同，TRPV 通道不是主要的电压门控通道。所有六种通道都具有独特的特性，对几种内源性配体以及不同的门控刺激（如热、pH 值、机械应力或渗透压变化）作出反应。它们的生理功能非常多样化，并且具有亚型和组织特异性。在许多组织中，它们作为不同疼痛刺激（热、压力、pH 值）的传感器，并有助于电解质的内稳态、屏障功能的维持和巨噬细胞的发育。由于它们在多种生理和病理生理过程中的基本作用，TRPV 通道是药物开发的有前途的靶点。然而，针对特定 TRPV 通道的药物（适合药物治疗）很少。此外，用于进一步研究 TRPV 通道的选择性和有效化合物通常缺乏。在这篇综述中，总结了 TRPV 通道的结构、不同的门控刺激、表达模式、生理和病理生理作用以及合成、天然和内源性配体的调节机制等不同方面。
