ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2
ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2
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DOI：
10.1046/j.1460-9568.2002.02253.x
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发表时间：
2002-11-01
影响因子：
3.4
通讯作者：
McCleskey, EW
中科院分区：
文献类型：
--
作者：
Molliver, DC;Cook, SP;McCleskey, EW
细胞外三磷酸腺苷通过开放三磷酸腺苷门控离子通道(P2X受体)迅速兴奋伤害性感觉神经元。在这里，我们描述了ATP和UTP对大鼠感觉神经元的两种相对缓慢和持续的作用：转录因子CREB的磷酸化和在去除配体后持续数十秒的延迟动作电位放电。这些反应的药理学研究表明，它们是由代谢性受体P2Y2介导的，而不是由P2X受体介导的。CREB磷酸化发生在一小部分外周蛋白阳性神经元中，可能是无髓伤害性感受器。原位杂交分析显示，在感觉神经元中广泛表达P2Y2基因。CREB的磷酸化是由动作电位引起的钙内流和细胞内钙释放共同调节的。这些发现表明，P2Y2参与了ATP介导的感觉信号的转导，并可能参与伤害性感受器表型的活性依赖性调节。
Extracellular ATP rapidly excites nociceptive sensory neurons by opening ATP-gated ion channels (P2X receptors). Here, we describe two actions of both ATP and UTP on rat sensory neurons that are relatively slow and sustained: phosphorylation of the transcription factor CREB and delayed action potential firing that persists for tens of seconds after removal of the ligand. The pharmacology of these responses indicates that they are mediated by the metabotropic receptor P2Y2, and not by P2X receptors. CREB phosphorylation occurred in a subset of small peripherin-positive neurons likely to be unmyelinated nociceptors. In situ hybridization analysis revealed widespread expression of P2Y2 mRNA in sensory neurons. CREB phosphorylation is mediated by both action-potential-evoked calcium influx and calcium release from intracellular stores. These findings suggest that P2Y2 contributes to the transduction of ATP-mediated sensory signalling, and may be involved in the activity-dependent regulation of nociceptor phenotype.