Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons
Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons
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初级感觉神经元中代谢型 P2Y UTP 受体增强酸敏感离子通道活性
DOI：
10.1007/s11302-015-9479-y
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发表时间：
2016-03
影响因子：
3.5
通讯作者：
Hu Wang-Ping
中科院分区：
文献类型：
--
作者：
Ren Cuixia;Gan Xiong;Wu Jing;Qiu Chun-Yu;Hu Wang-Ping
外周嘌呤能信号在伤害感受中起重要作用。越来越多的证据表明，代谢型P2 Y受体也参与其中，但对潜在的机制知之甚少。在此，我们报道了选择性P2 Y受体激动剂5′-三磷酸尿苷（UTP）可增强大鼠背根神经节（DRG）神经元酸敏感离子通道（ASIC）的功能活性。首先，UTP剂量依赖性地增加ASIC电流的幅度。UTP还使质子的浓度-响应曲线上移，对质子的最大电流响应增加56.6 ± 6.4%。第二，UTP对质子门控电流的增强作用可以被ATP模拟，但不能被P2 Y1受体激动剂ADP模拟。通过抑制细胞内G蛋白、磷脂酶C（PLC）、蛋白激酶C（PKC）或与C-激酶1（PICK 1）相互作用的蛋白质信号传导，P2 Y受体拮抗剂苏拉明可阻断UTP的增强作用。第三，UTP改变了酸中毒诱发的DRG神经元膜兴奋性，并引起去极化幅度和由酸刺激引起的棘波数量的显着增加。最后，UTP剂量依赖性地加重大鼠对注射乙酸的伤害性反应。这些结果表明，UTP增强ASIC介导的电流和伤害性反应，这揭示了一个新的外周机制的UTP敏感的P2 Y2受体参与痛觉过敏的敏感性ASIC在初级感觉神经元。
Peripheral purinergic signaling plays an important role in nociception. Increasing evidence suggests that metabotropic P2Y receptors are also involved, but little is known about the underlying mechanism. Herein, we report that selective P2Y receptor agonist uridine 5′-triphosphate (UTP) can exert an enhancing effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglia (DRG) neurons. First, UTP dose-dependently increased the amplitude of ASIC currents. UTP also shifted the concentration–response curve for proton upwards, with a 56.6 ± 6.4 % increase of the maximal current response to proton. Second, UTP potentiation of proton-gated currents can be mimicked by adenosine 5′-triphosphate (ATP), but not by P2Y1 receptor agonist ADP. Potentiation of UTP was blocked by P2Y receptor antagonist suramin and by inhibition of intracellular G protein, phospholipase C (PLC), protein kinase C (PKC), or protein interacting with C-kinase 1 (PICK1) signaling. Third, UTP altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, UTP dose-dependently exacerbated nociceptive responses to injection of acetic acid in rats. These results suggest that UTP enhanced ASIC-mediated currents and nociceptive responses, which reveal a novel peripheral mechanism underlying UTP-sensitive P2Y2receptor involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.
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血清素以依赖于 ASIC3 通道的非质子配体传感域的方式促进外周疼痛敏感性
影响因子：
5.3
作者：
Wang Xiang;Li Wei-Guang;Yu Ye;Xiao Xian;Cheng Jin;Zeng Wei-Zheng;Peng Zhong;Zhu Michale Xi;Xu Tian-Le
通讯作者：
Xu Tian-Le
影响因子：
34.7
作者：
Wemmie, John A.;Taugher, Rebecca J.;Kreple, Collin J.
通讯作者：
Kreple, Collin J.
DOI：
10.1113/jphysiol.2009.175059
发表时间：
2009-07-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Lechner SG;Lewin GR
通讯作者：
Lewin GR
影响因子：
--
作者：
S. P. Sutherland;S. Cook;E. McCleskey
通讯作者：
S. P. Sutherland;S. Cook;E. McCleskey
影响因子：
7.4
作者：
Malin, Sacha A.;Davis, Brian M.;Molliver, Derek C.
通讯作者：
Molliver, Derek C.