Division of Clinical Physiology, Institute of CardiologyDepartment of PhysiologyDepartment of Pharmacology and Pharmacotherapy, Institute of PharmacologyDepartment of OphthalmologyResearch Centre for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Br J Pharmacol. 2012 Mar;165(6):1801-1812. doi: 10.1111/j.1476-5381.2011.01645.x.
The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor.
Sensory TRPV1 activation was measured in rats by use of an eye wiping assay. Arteriolar TRPV1-mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca(2+)) were determined in isolated, pressurized skeletal muscle arterioles obtained from the rat and wild-type or TRPV1(-/-) mice and in canine isolated smooth muscle cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in rat isolated skeletal muscle arteries.
Capsaicin evoked a constrictor response in isolated arteries similar to that mediated by noradrenaline, this was absent in arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist AMG9810. Capsaicin increased intracellular Ca(2+) in the arteriolar wall and in isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular constrictions (MSK-195 and JYL-79) or were without effect (resiniferatoxin and JYL-273), although all increased the number of responses (sensory activation) in the eye wiping assay. Maximal doses of all agonists induced complete desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of capsaicin). Responses to the partial agonist JYL-1511 suggested 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation.
Arteriolar TRPV1 have different pharmacological properties from those located on sensory neurons in the rat.
瞬时受体电位香草素 1（TRPV1）在各种痛觉刺激激活感觉神经元中发挥作用，是一种治疗靶点。然而，在外周动脉中也表达了功能性 TRPV1，它影响微血管直径，我们试图对其进行表征。
使用眨眼试验测量大鼠中感觉 TRPV1 的激活。在从大鼠和野生型或 TRPV1（-/-）小鼠中获得的分离加压骨骼肌动脉中以及在犬分离的平滑肌细胞中，测定了动脉血管 TRPV1 介导的平滑肌特异性反应（小动脉直径，细胞内 Ca(2+)变化）。在大鼠分离的骨骼肌动脉中测定 TRPV1 激动剂的血管药理学（效力、功效、作用动力学和受体脱敏）。
辣椒素在分离的动脉中引起类似于去甲肾上腺素介导的收缩反应，这种反应在 TRPV1 敲除小鼠的动脉中不存在，并被 TRPV1 拮抗剂 AMG9810 竞争性抑制。辣椒素增加了小动脉壁和分离的平滑肌细胞中的细胞内 Ca(2+)。TRPV1 激动剂引起类似的血管收缩（MSK-195 和 JYL-79）或没有作用（树脂毒素和 JYL-273），尽管所有激动剂都增加了眨眼试验中的反应数量（感觉激活）。所有激动剂的最大剂量都诱导了小动脉 TRPV1 的完全脱敏（快速耐受）（除了辣椒素）。部分激动剂 JYL-1511 的反应表明，10%的 TRPV1 激活足以引起血管快速耐受而不引起感觉激活。
大鼠中动脉血管的 TRPV1 具有与感觉神经元中不同的药理学特性。
