Sensitization of vanilloid receptor 1 induced by bradykinin via the activation of second messenger signaling cascades in rat primary afferent neurons
Sensitization of vanilloid receptor 1 induced by bradykinin via the activation of second messenger signaling cascades in rat primary afferent neurons
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DOI：
10.1016/j.ejphar.2004.07.076
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发表时间：
2004-09-13
影响因子：
5
通讯作者：
Nakata, Y
中科院分区：
文献类型：
--
作者：
Tang, HB;Inoue, A;Nakata, Y
香草酸受体1最近被报道在痛觉过敏中起重要作用，但该受体被内源性炎症介质如缓激肽和神经生长因子激活的机制尚未完全清楚。在这里，我们研究了产生疼痛的炎症介质缓激肽是否通过诱导大鼠背根神经节细胞环氧合酶、磷脂酶C和磷脂酶A(2)的激活而增敏香草素受体1。我们用Ca-45(2+)摄取和肌醇磷酸蓄积实验证明了这一点，缓激肽通过缓激肽B-2受体激活磷脂酶C和环氧合酶-1。然后，缓激肽B-2受体通过促进非选择性钙通道活动，增加细胞外池中的细胞内钙离子浓度，从而敏化香草素受体1的活性。这些方法将有助于筛选具有香草素受体1活性的新药。这些数据表明，由几种酶产生的内源性物质可能能够产生涉及香草素受体1的协同反应。(C)2004爱思唯尔公司保留所有权利。
Vanilloid receptor 1 was recently reported to play an important role in hyperalgesia, but the mechanisms by which this receptor is activated by endogenous inflammatory mediators, such as bradykinin and nerve growth factor, are not yet fully understood. Here, we investigated whether bradykinin, which is a pain-producing inflammatory mediator, sensitizes vanilloid receptor 1 by inducing the activation of cyclooxygenases, phospholipase C and phospholipase A(2) in rat dorsal root ganglion cells. We demonstrated this using Ca-45(2+) uptake and inositol phosphates accumulation assays, bradykinin activates phospholipase C and cyclooxygenase-1 through the bradykinin B-2 receptor. The bradykinin B-2 receptor then sensitizes vanilloid receptor 1 activity by facilitating non-selective Ca2+ channel activity, increasing the intracellular Ca2+ concentration from the extracellular pool. These methods would be useful for screening new drugs for activity at vanilloid receptor 1. These data suggest that endogenous substances produced by several enzymes may be capable of producing a synergistic response involving the vanilloid receptor 1. (C) 2004 Elsevier B.V. All rights reserved.