Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons
Morphine inhibits acid-sensing ion channel currents in rat dorsal root ganglion neurons
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DOI：
10.1016/j.brainres.2014.01.042
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发表时间：
2014-03-20
期刊：
影响因子：
2.9
通讯作者：
Hu, Wang-Ping
中科院分区：
文献类型：
--
作者：
Cai, Qi;Qiu, Chun-Yu;Hu, Wang-Ping
细胞外酸中毒是产生疼痛的病理条件中的常见特征。酸敏感离子通道（Acid-sensing ion channels，ASIC）是分布于外周感觉神经元的pH传感器，参与伤害性感受。吗啡通过激活阿片受体对各种疼痛状况发挥有效的镇痛作用。到目前为止，尚未显示ASIC与外周感觉神经元中的阿片受体之间的串扰。在这里，我们发现吗啡抑制大鼠背根神经节（DRG）神经元中天然ASIC的活性。吗啡剂量依赖性抑制质子门控电流的ASIC介导的TRPV 1抑制剂辣椒平的存在。吗啡使质子浓度-响应曲线下移，最大电流响应降低51.4 ± 3.8%，但pH值（0.5）无显著变化。与吗啡相比，另一种μ阿片受体激动剂DAMGO诱导了类似的ASIC电流降低。吗啡对ASIC电流的抑制可被特异性阿片受体拮抗剂纳洛酮阻断。预处理forskolin，腺苷酸环化酶激活剂，或添加cAMP逆转吗啡的抑制作用。此外，吗啡改变了大鼠背根神经节神经元酸诱发的兴奋性，减少了由酸刺激引起的动作电位的数量。外周应用吗啡可减轻大鼠足底注射醋酸引起的疼痛。以上结果提示吗啡可通过It-阿片受体和cAMP依赖的信号通路抑制ASICs的活性。这些观察结果表明，ASIC和阿片受体之间的外周感觉神经元的串扰，这是一个新的吗啡镇痛机制。(c)2014爱思唯尔有限公司版权所有。
Extracellular acidosis is a common feature in pain-generating pathological conditions. Acid-sensing ion channels (ASICs), pH sensors, are distributed in peripheral sensory neurons and participate in nociception. Morphine exerts potent analgesic effects through the activation of opioid receptors for various pain conditions. A cross-talk between ASICs and opioid receptors in peripheral sensory neurons has not been shown so far. Here, we have found that morphine inhibits the activity of native ASICs in rat dorsal root ganglion (DRG) neurons. Morphine dose-dependently inhibited proton-gated currents mediated by ASICs in the presence of the TRPV1 inhibitor capsazepine. Morphine shifted the proton concentration-response curve downwards, with a decrease of 51.4 +/- 3.8% in the maximum current response but with no significant change in the pH(0.5) value. Another mu-opioid receptor agonist DAMGO induced a similar decrease in ASIC currents compared with morphine. The morphine inhibition of ASIC currents was blocked by naloxone, a specific opioid receptor antagonist. Pretreatment of forskolin, an adenylyl cyclase activator, or the addition of cAMP reversed the inhibitory effect of morphine. Moreover, morphine altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. Finally, peripheral applied morphine relieved pain evoked by intraplantar of acetic acid in rats. Our results indicate that morphine can inhibit the activity of ASICs via It-opioid receptor and cAMP dependent signal pathway. These observations demonstrate a cross-talk between ASICs and opioid receptors in peripheral sensory neurons, which was a novel analgesic mechanism of morphine. (c) 2014 Elsevier B.V. All rights reserved.