Oxytocin inhibits the activity of acid-sensing ion channels through the vasopressin, V1A receptor in primary sensory neurons
Oxytocin inhibits the activity of acid-sensing ion channels through the vasopressin, V1A receptor in primary sensory neurons
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催产素通过初级感觉神经元中的加压素、V1A 受体抑制酸敏感离子通道的活性
DOI：
10.1111/bph.12635
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发表时间：
2014-06-01
影响因子：
7.3
通讯作者：
Hu, Wang-Ping
中科院分区：
文献类型：
--
作者：
Qiu, Fang;Qiu, Chun-Yu;Hu, Wang-Ping
背景与目的越来越多的研究表明，催产素（OT）在痛觉调制中具有镇痛作用。迄今为止，大多数工作都集中在OT镇痛的中枢机制，但很少有人知道外周机制是否也参与其中。酸敏感离子通道（ASIC）分布在外周感觉神经元中并参与伤害性感受。本研究观察了OT对背根神经节（DRG）神经元ASICs活性的影响。实验方法采用大鼠背根节神经元进行电生理实验。在缺乏加压素V1 A受体的大鼠和小鼠中，乙酸诱导了伤害性行为。关键结果OT抑制天然ASIC的功能活性。首先，OT剂量依赖性地降低DRG神经元ASIC电流的幅度。其次，OT对ASIC电流的抑制作用可被精氨酸加压素（AVP）模拟，并可被V1 A受体拮抗剂SR 49059完全阻断，但不能被OT受体拮抗剂L-368899阻断。第三，OT改变了酸刺激引起的DRG神经元膜兴奋性，显著降低了酸刺激引起的去极化幅度和动作电位数目。最后，外周给药OT或AVP抑制大鼠足底注射乙酸的伤害性反应。OT和AVP对野生型小鼠酸中毒诱发的疼痛也有镇痛作用，但对V-1A受体敲除小鼠无此作用。结论和影响这些结果揭示了一种新的外周机制OT的镇痛作用涉及调制的本地ASIC在初级感觉神经元V-1A受体介导的。
Background and Purpose A growing number of studies have demonstrated that oxytocin (OT) plays an analgesic role in modulation of nociception and pain. Most work to date has focused on the central mechanisms of OT analgesia, but little is known about whether peripheral mechanisms are also involved. Acid-sensing ion channels (ASICs) are distributed in peripheral sensory neurons and participate in nociception. Here, we investigated the effects of OT on the activity of ASICs in dorsal root ganglion (DRG) neurons. Experimental Approach Electrophysiological experiments were performed on neurons from rat DRG. Nociceptive behaviour was induced by acetic acid in rats and mice lacking vasopressin, V1A receptors. Key Results OT inhibited the functional activity of native ASICs. Firstly, OT dose-dependently decreased the amplitude of ASIC currents in DRG neurons. Secondly, OT inhibition of ASIC currents was mimicked by arginine vasopressin (AVP) and completely blocked by the V1A receptor antagonist SR49059, but not by the OT receptor antagonist L-368899. Thirdly, OT altered acidosis-evoked membrane excitability of DRG neurons and significantly decreased the amplitude of the depolarization and number of action potentials induced by acid stimuli. Finally, peripherally administered OT or AVP inhibited nociceptive responses to intraplantar injection of acetic acid in rats. Both OT and AVP also induced an analgesic effect on acidosis-evoked pain in wild-type mice, but not in V-1A receptor knockout mice. Conclusions and Implications These results reveal a novel peripheral mechanism for the analgesic effect of OT involving the modulation of native ASICs in primary sensory neurons mediated by V-1A receptors.