Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons.
Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons.
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Prokineticin 2 增强大鼠背根神经节神经元的酸敏感离子通道活性。
DOI：
10.1186/1742-2094-9-108
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发表时间：
2012-05-29
影响因子：
9.3
通讯作者：
Hu WP
中科院分区：
文献类型：
--
作者：
Qiu CY;Liu YQ;Qiu F;Wu J;Zhou QY;Hu WP
Prokineticin 2 （PK2）是一种分泌蛋白，在体内引起强效痛觉过敏，因此被认为是一种新的前感觉介质。然而，PK2产生前感觉作用的分子靶点仍然知之甚少。在这里，我们发现PK2增强了初级感觉神经元中酸感应离子通道的活性。本研究采用全细胞膜片钳和电压钳记录技术对刚从大鼠背根神经节分离的神经元进行实验。PK2剂量依赖性增强质子门控电流，EC50为0.22±0.06 nM。PK2使质子浓度-响应曲线向上移动，最大电流响应增加1.81±0.11倍。PK2受体拮抗剂完全阻断PK2对质子门控电流的增强作用。细胞内透析GF109203X（一种蛋白激酶C抑制剂）或FSC-231（一种与C激酶1抑制剂相互作用的蛋白）也能消除这种增强作用。PK2增强了大鼠背根神经节神经元的酸诱发膜兴奋性，并引起酸刺激引起的去极化振幅和尖峰数的显著增加。最后，PK2加重了大鼠对醋酸注射的伤害性反应。这些结果表明，PK2通过PK2受体和蛋白激酶c依赖的信号通路增加了大鼠初级感觉神经元中酸感离子通道的活性。我们的研究结果支持PK2是一种促痛因子，其信号可能通过敏化酸敏感离子通道参与酸中毒引起的疼痛。
Prokineticin 2 (PK2) is a secreted protein and causes potent hyperalgesia in vivo, and is therefore considered to be a new pronociceptive mediator. However, the molecular targets responsible for the pronociceptive effects of PK2 are still poorly understood. Here, we have found that PK2 potentiates the activity of acid-sensing ion channels in the primary sensory neurons. In the present study, experiments were performed on neurons freshly isolated from rat dorsal root ganglion by using whole-cell patch clamp and voltage-clamp recording techniques. PK2 dose-dependently enhanced proton-gated currents with an EC50 of 0.22 ± 0.06 nM. PK2 shifted the proton concentration-response curve upwards, with a 1.81 ± 0.11 fold increase of the maximal current response. PK2 enhancing effect on proton-gated currents was completely blocked by PK2 receptor antagonist. The potentiation was also abolished by intracellular dialysis of GF109203X, a protein kinase C inhibitor, or FSC-231, a protein interacting with C-kinase 1 inhibitor. Moreover, PK2 enhanced the acid-evoked membrane excitability of rat dorsal root ganglion neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, PK2 exacerbated nociceptive responses to the injection of acetic acid in rats. These results suggest that PK2 increases the activity of acid-sensing ion channels via the PK2 receptor and protein kinase C-dependent signal pathways in rat primary sensory neurons. Our findings support that PK2 is a proalgesic factor and its signaling likely contributes to acidosis-evoked pain by sensitizing acid-sensing ion channels.
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影响因子：
7.3
作者：
Negri, L;Lattanzi, R;Melchiorri, P
通讯作者：
Melchiorri, P
影响因子：
11.4
作者：
Deval, Emmanuel;Noel, Jacques;Lingueglia, Eric
通讯作者：
Lingueglia, Eric
影响因子：
2.9
作者：
Omori, Megumi;Yokoyama, Masataka;Ichikawa, Hiroyuki
通讯作者：
Ichikawa, Hiroyuki
影响因子：
3.3
作者：
Hu WP;Zhang C;Li JD;Luo ZD;Amadesi S;Bunnett N;Zhou QY
通讯作者：
Zhou QY
影响因子：
4
作者：
Negri, Lucia;Lattanzi, Roberta
通讯作者：
Lattanzi, Roberta