Effects of prostaglandin D2 on tetrodotoxin-resistant Na+ currents in DRG neurons of adult rat
Effects of prostaglandin D2 on tetrodotoxin-resistant Na+ currents in DRG neurons of adult rat
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DOI：
10.1016/j.pain.2011.01.033
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发表时间：
2011-05-01
期刊：
影响因子：
7.4
通讯作者：
Schaible, Hans-Georg
中科院分区：
文献类型：
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作者：
Ebersberger, Andrea;Natura, Gabriel;Schaible, Hans-Georg
河豚毒素抗性（TTX-R）Na+通道在伤害性背根神经节（DRG）神经元中动作电位的产生中起关键作用，并且是促炎介质前列腺素E-2的重要靶点，前列腺素E-2增强这些电流。前列腺素D-2（PGD（2））与前列腺素E-2一起在组织中释放，据报道它是可抑制的，但其对初级传入神经元的影响尚不清楚。在本研究中，我们在DRG神经元中定位了G（s）-蛋白偶联的DP 1和G（i）-蛋白偶联的DP 2受体，并在膜片钳记录中评估了PGD（2）对成年大鼠培养的中小型DRG神经元TTX-R Na+电流的影响。DP 1和DP 2受体样免疫反应位于绝大多数DRG神经元。在所有神经元中，PGD（2）将电导转移到更高的超极化电位，这取决于Na（v）1.9通道的作用。在大约三分之一的神经元中，PGD（2）还通过促进电导和增加最大电流幅度来影响Na（v）1.8通道。选择性DP 1受体激活可增加大多数神经元TTX-R Na+电流的振幅，但这种作用被DP 2受体激活所抵消，而DP 2受体激活本身没有影响。在电流钳模式下，PGD（2）降低了动作电位诱发的阈值，并增加了每次刺激的动作电位数量，这一效应主要取决于DP 1受体激活。因此，PGD（2）对DRG神经元的净效应是原伤害感受性的，尽管TTX-R Na+电流的大小取决于DP 1和DP 2受体激活的平衡。(C)2011年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Tetrodotoxin-resistant (TTX-R) Na+ channels play a key role in the generation of action potentials in nociceptive dorsal root ganglion (DRG) neurons and are an important target for the proinflammatory mediator prostaglandin E-2, which augments these currents. Prostaglandin D-2 (PGD(2)) is released in the tissue together with prostaglandin E-2, and it was reported to be antiinflammatory, but its effect on primary afferent neurons is unclear. In the present study we localised G(s)-protein-coupled DP1 and G(i)-protein-coupled DP2 receptors in DRG neurons, and we assessed the effect of PGD(2) on TTX-R Na+ currents in patch-clamp recordings from small-to medium-sized cultured DRG neurons from adult rats. DP1 and DP2 receptor-like immunoreactivity was localised in the vast majority of DRG neurons. In all neurons, PGD(2) shifted conductance to more hyperpolarised potentials, depending on an action at Na(v)1.9 channels. In about one third of the neurons, PGD(2) additionally influenced Na(v)1.8 channels by facilitating conductance and by increasing maximal current amplitudes. Selective DP1 receptor activation increased the amplitude of TTX-R Na+ currents of most neurons, but this effect was counteracted by DP2 receptor activation, which by itself had no effect. In the current-clamp mode, PGD(2) lowered the threshold for elicitation of an action potential and increased the number of action potentials per stimulus, an effect mainly depending on DP1 receptor activation. Thus, the net effect of PGD(2) on DRG neurons is pronociceptive, although the magnitude of the TTX-R Na+ currents depends on the balance of DP1 and DP2 receptor activation. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.