Wang Donna H
Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48825, USA.
Acta Pharmacol Sin. 2005 Mar;26(3):286-94. doi: 10.1111/j.1745-7254.2005.00057.x.
Mammalian transient receptor potential (TRP) channels consist of six related protein sub-families that are involved in a variety of pathophysiological function, and disease development. The TRPV1 channel, a member of the TRPV sub-family, is identified by expression cloning using the "hot" pepper-derived vanilloid compound capsaicin as a ligand. Therefore, TRPV1 is also referred as the vanilloid receptor (VR1) or the capsaicin receptor. VR1 is mainly expressed in a subpopulation of primary afferent neurons that project to cardiovascular and renal tissues. These capsaicin-sensitive primary afferent neurons are not only involved in the perception of somatic and visceral pain, but also have a "sensory-effector" function. Regarding the latter, these neurons release stored neuropeptides through a calcium-dependent mechanism via the binding of capsaicin to VR1. The most studied sensory neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are potent vasodilators and natriuretic/diuretic factors. Recent evidence using the model of neonatal degeneration of capsaicin-sensitive sensory nerves revealed novel mechanisms that underlie increased salt sensitivity and several experimental models of hypertension. These mechanisms include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin-1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance the prohypertensive effects of several neurohormonal systems to maintain normal blood pressure when challenged with salt loading. The therapeutic utilities of vanilloid compounds, endogenous agonists, and sensory neuropeptides are also discussed.
哺乳动物瞬时受体电位(TRP)通道由六个相关的蛋白质亚家族组成,它们参与多种病理生理功能和疾病发展。TRPV1通道是TRPV亚家族的成员,通过使用源自“辣”椒的香草素化合物辣椒素作为配体进行表达克隆来鉴定。因此,TRPV1也被称为香草素受体(VR1)或辣椒素受体。VR1主要表达于投射至心血管和肾脏组织的初级传入神经元亚群中。这些对辣椒素敏感的初级传入神经元不仅参与躯体和内脏疼痛的感知,还具有“感觉-效应器”功能。关于后者,这些神经元通过辣椒素与VR1结合,经由钙依赖机制释放储存的神经肽。研究最多的感觉神经肽是降钙素基因相关肽(CGRP)和P物质(SP),它们是强效血管舒张剂和利钠/利尿因子。最近使用辣椒素敏感感觉神经新生期退变模型的证据揭示了盐敏感性增加和几种高血压实验模型背后的新机制。这些机制包括盐负荷后血浆肾素活性和血浆醛固酮水平的抑制不足、面对盐刺激时交感兴奋反应增强、内皮素-1受体激活以及辣椒素预处理大鼠对盐负荷的利钠反应受损。这些数据表明,感觉神经在受到盐负荷挑战时会抵消几种神经激素系统的升压作用,以维持正常血压。还讨论了香草素化合物、内源性激动剂和感觉神经肽的治疗用途。