Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia
Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia
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DOI：
10.1073/pnas.111025298
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发表时间：
2001-05
影响因子：
11.1
通讯作者：
M. Tominaga;M. Wada;M. Masu
中科院分区：
文献类型：
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作者：
M. Tominaga;M. Wada;M. Masu
辣椒素（香草素）受体VR1是一种感觉神经元特异性离子通道，作为产生疼痛的化学和物理刺激的多模态检测器。已经提出，ATP，从不同类型的细胞释放，通过主要作用于位于感觉神经末梢的痛觉性嗜离子嘌呤感受器，引发疼痛的感觉。在这项研究中，我们研究了细胞外ATP对VR1的影响。在表达VR1的细胞中，ATP通过在蛋白激酶c依赖通路中激活代谢性P2Y1受体，增加了辣椒素或质子引起的电流。在表达VR1和M1毒蕈碱乙酰胆碱受体的细胞中证实了Gq/11偶联代谢受体参与VR1反应的增强。在ATP存在的情况下，VR1激活的温度阈值从42°C降低到35°C，这样通常无痛感的热刺激（即正常体温）能够激活VR1。这代表了一种新的机制，通过这种机制，在组织创伤的反应中，受损细胞释放的大量ATP可能会引发疼痛的感觉。
The capsaicin (vanilloid) receptor, VR1, is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been proposed that ATP, released from different cell types, initiates the sensation of pain by acting predominantly on nociceptive ionotropic purinoceptors located on sensory nerve terminals. In this study, we examined the effects of extracellular ATP on VR1. In cells expressing VR1, ATP increased the currents evoked by capsaicin or protons through activation of metabotropic P2Y1 receptors in a protein kinase C-dependent pathway. The involvement of Gq/11-coupled metabotropic receptors in the potentiation of VR1 response was confirmed in cells expressing both VR1 and M1 muscarinic acetylcholine receptors. In the presence of ATP, the temperature threshold for VR1 activation was reduced from 42°C to 35°C, such that normally nonpainful thermal stimuli (i.e., normal body temperature) were capable of activating VR1. This represents a novel mechanism through which the large amounts of ATP released from damaged cells in response to tissue trauma might trigger the sensation of pain.