The transient receptor potential vanilloid subfamily member 1 (TRPV1) is a protein mainly expressed in sensory neurons and fibers, such as in trigeminal ganglion and dorsal root ganglion, and has been indicated to be involved in several physiological and pathological processes. Studies on thermal activation have revealed that phosphorylation is involved in TRPV1 activation and 2 putative phosphorylation sites, Ser residues 502 (Ser-502) and Ser residues 800 (Ser-800), have been recently confirmed to possess the capability of resensitizing TRPV1. In addition to acidification, alkalization has also been proved to be a highly effective stimulator for TRPV1. TRPV1 could be regulated by various physical and chemical modulators, as well as the chronic pain. TRPV1 plays a crucial role in the transmission of pain signals, especially under inflammation and the neoplasm conditions, and it can also modulate nociceptive afferents by reinforcing morphine tolerance. The present review mainly focused on the structural and functional complexities of TRPV1, together with its activation and modulation by a wide variety of physical and chemical stimuli. Its pharmacological manipulation (sensitization/desensitization) and therapeutical targets were also discussed.
瞬时受体电位香草酸受体1 (transient receptor potential vanilloid subfamily member 1, TRPV1) 主要表达于感觉神经元及其纤维, 如背根神经节和三叉神经节, 并参与多种生理病理过程。对热刺激的研究使得细胞磷酸化水平在TRPV1活化过程中的作用被逐渐认识。最新的分子学实验发现了 TRPV1 磷酸化的两个新位点, 即 Ser-502 (Ser residues 502) 和 Ser-800 (Ser residues 800) 位点, 两者都具有使失活的 TRPV1 通道重活化的作用。另外, 继酸被发现可以激活TRPV1 后, 目前碱也被证实是一种高效的TRPV1 刺激因子。研究发现TRPV1 在神经系统疼痛信号传导整合中发挥重要作用, 尤其是在炎症或肿瘤情况下。吗啡耐受作用的加强也被认为是 TRPV1 介导的疼痛信号的调节机制之一。本文主要对TRPV1 的结构、表达、激活及调节因素作一综述, 并对 TRPV1 在生理与病理条件下的活动改变及其机制, 以及 TRPV1 相关的新药理学和治疗靶点进行了讨论。