缓激肽-12-脂氧合酶-VR1信号通路与炎性痛觉过敏
Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia.
作者信息
Shin Jieun, Cho Hawon, Hwang Sun Wook, Jung Jooyoung, Shin Chan Young, Lee Soon-Youl, Kim So Hee, Lee Myung Gull, Choi Young Hae, Kim Jinwoong, Haber Nicole Alessandri, Reichling David B, Khasar Sachia, Levine Jon D, Oh Uhtaek
机构信息
Sensory Research Center, National Creative Research Initiatives, Seoul National University, San 56-1, Shinlim, Kwanak-Gu, Seoul 151-742, Korea.
出版信息
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10150-5. doi: 10.1073/pnas.152002699. Epub 2002 Jul 3.
Abstract
The capsaicin-sensitive vanilloid receptor (VR1) was recently shown to play an important role in inflammatory pain (hyperalgesia), but the underlying mechanism is unknown. We hypothesized that pain-producing inflammatory mediators activate capsaicin receptors by inducing the production of fatty acid agonists of VR1. This study demonstrates that bradykinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid. This finding identifies a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain.
摘要
辣椒素敏感的香草酸受体（VR1）最近被证明在炎性疼痛（痛觉过敏）中起重要作用，但其潜在机制尚不清楚。我们推测，产生疼痛的炎性介质通过诱导VR1的脂肪酸激动剂生成来激活辣椒素受体。本研究表明，缓激肽作用于B2缓激肽受体，通过花生四烯酸的12-脂氧合酶代谢产物的生成激活辣椒素受体，从而使感觉神经末梢兴奋。这一发现确定了一种机制，可能成为开发治疗炎性疼痛新策略的靶点。
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1
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Nature. 2001 Jun 21;411(6840):957-62. doi: 10.1038/35082088.
2
Sustained sensitization and recruitment of rat cutaneous nociceptors by bradykinin and a novel theory of its excitatory action.缓激肽对大鼠皮肤伤害感受器的持续致敏和募集作用及其兴奋作用的新理论
J Physiol. 2001 Apr 1;532(Pt 1):229-39. doi: 10.1111/j.1469-7793.2001.0229g.x.
3
Increased levels of 12(S)-HETE in patients with essential hypertension.原发性高血压患者中12(S)-羟基二十碳四烯酸水平升高。
Hypertension. 2001 Feb;37(2):334-8. doi: 10.1161/01.hyp.37.2.334.
4
Induction of vanilloid receptor channel activity by protein kinase C.蛋白激酶C对香草酸受体通道活性的诱导作用。
Nature. 2000;408(6815):985-90. doi: 10.1038/35050121.
5
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Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13889-94. doi: 10.1073/pnas.230146497.
6
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Toxicol Appl Pharmacol. 2000 Nov 15;169(1):66-76. doi: 10.1006/taap.2000.9040.
7
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Proc Natl Acad Sci U S A. 2000 May 23;97(11):6155-60. doi: 10.1073/pnas.97.11.6155.
8
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9
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