ORL1 receptor-mediated internalization of N-type calcium channels
ORL1 receptor-mediated internalization of N-type calcium channels
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DOI：
10.1038/nn1605
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发表时间：
2006-01-01
影响因子：
25
通讯作者：
Zamponi, GW
中科院分区：
文献类型：
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作者：
Altier, C;Khosravani, H;Zamponi, GW
阿片受体样受体1（ORL1）对N型钙通道的抑制是控制伤害性信息传递的重要机制。我们最近报道了由ORL 1受体和N型通道组成的信号复合物介导钙离子进入的紧张性抑制。在这里，我们表明，延长（类似于30分钟）的ORL 1受体暴露于其激动剂痛敏素触发这些信号复合物的内化到囊泡隔室。这种效应依赖于蛋白激酶C的激活，选择性地发生在N型通道上，并且不能在μ阿片或血管紧张素受体上观察到。在表达系统和大鼠背根神经节神经元中，痛敏肽介导的通道内化伴随着钙离子进入的显著下调，这与从质膜选择性去除N型钙通道平行。这可能为长期调节疼痛通路中的钙进入提供了新的手段。
The inhibition of N-type calcium channels by opioid receptor like receptor 1 (ORL1) is a key mechanism for controlling the transmission of nociceptive signals. We recently reported that signaling complexes consisting of ORL1 receptors and N-type channels mediate a tonic inhibition of calcium entry. Here we show that prolonged (similar to 30 min) exposure of ORL1 receptors to their agonist nociceptin triggers an internalization of these signaling complexes into vesicular compartments. This effect is dependent on protein kinase C activation, occurs selectively for N-type channels and cannot be observed with mu-opioid or angiotensin receptors. In expression systems and in rat dorsal root ganglion neurons, the nociceptin-mediated internalization of the channels is accompanied by a significant downregulation of calcium entry, which parallels the selective removal of N-type calcium channels from the plasma membrane. This may provide a new means for long-term regulation of calcium entry in the pain pathway.