Possible involvement of P2Y2 metabotropic receptors in ATP-Induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity
Possible involvement of P2Y2 metabotropic receptors in ATP-Induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity
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DOI：
10.1523/jneurosci.23-14-06058.2003
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发表时间：
2003-07-09
影响因子：
5.3
通讯作者：
Tominaga, M
中科院分区：
文献类型：
--
作者：
Moriyama, T;Iida, T;Tominaga, M
辣椒素受体瞬时受体电位V1 （TRPV1，也称为香草受体1）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。据报道，胞外ATP增强了辣椒素或质子引起的TRPV1电流，并在pkc依赖的途径中通过代谢P2Y受体降低了其激活的温度阈值，这表明TRPV1的激活可以在ATP存在的正常体温下触发痛觉。本研究表明，在缺乏TRPV1的小鼠中，ATP诱导的热痛觉过敏被消除，这表明ATP和TRPV1在行为水平上存在功能相互作用。然而，P2Y(1)受体缺陷小鼠的热痛觉过敏仍然存在。小鼠背根神经节神经元膜片钳分析显示P2Y(2)而不是P2Y(1)受体参与。采用原位杂交组织化学方法测定大鼠腰椎DRG组织中TRPV1 mRNA与P2Y(2) mRNA共表达，而非P2Y(1) mRNA共表达。这些数据表明代谢P2Y(2)受体通过TRPV1在伤害感受中的重要性。
The capsaicin receptor transient receptor potential V1 (TRPV1; also known as vanilloid receptor 1) is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been reported that extracellular ATP potentiates the TRPV1 currents evoked by capsaicin or protons and reduces the temperature threshold for its activation through metabotropic P2Y receptors in a PKC-dependent pathway, suggesting that TRPV1 activation could trigger the sensation of pain at normal body temperature in the presence of ATP. Here, we show that ATP-induced thermal hyperalgesia was abolished in mice lacking TRPV1, suggesting the functional interaction between ATP and TRPV1 at a behavioral level. However, thermal hyperalgesia was preserved in P2Y(1) receptor-deficient mice. Patch-clamp analyses using mouse dorsal root ganglion neurons indicated the involvement of P2Y(2) rather than P2Y(1) receptors. Coexpression of TRPV1 mRNA with P2Y(2) mRNA, but not P2Y(1) mRNA, was determined in the rat lumbar DRG using in situ hybridization histochemistry. These data indicate the importance of metabotropic P2Y(2) receptors in nociception through TRPV1.