ATP is a mediator of chemosensory transduction in the central nervous system
ATP is a mediator of chemosensory transduction in the central nervous system
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DOI：
10.1038/nature03690
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发表时间：
2005-07-07
期刊：
影响因子：
64.8
通讯作者：
Spyer, KM
中科院分区：
文献类型：
--
作者：
Gourine, AV;Llaudet, E;Spyer, KM
嘌呤核苷酸ATP的细胞外信号传导长期以来与感觉功能相关（1-8）。在外周，ATP介导伤害感受（3-5）、机械敏感性（3，6）、热敏感性（7）和O-2化学敏感性（8）。这些过程共享一个共同的机制，涉及ATP的释放，通过激活离子型P2 X和/或代谢型P2 Y受体来兴奋传入纤维。位于脑干中的化学传感器对于通过呼吸调节维持血气的生理水平至关重要（9-11）。在这里，我们表明，在动脉血中的p（CO 2）的增加触发立即释放ATP从位于延髓腹侧表面的三个化学敏感区域。阻断这些部位的ATP受体减少了呼吸的化学感觉控制，表明ATP释放构成了中枢化学感觉转导的关键步骤。这些新的数据表明，ATP，一种遗传学上古老的，独特的和简单的分子，已被广泛用于传入系统的进化，不仅在外周，而且在中枢神经系统内介导不同形式的感觉转导。
Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function(1-8). In the periphery, ATP mediates nociception(3-5), mechanosensitivity(3,6), thermal sensitivity(7) and O-2 chemosensitivity(8). These processes share a common mechanism that involves the release of ATP to excite afferent fibres via activation of ionotropic P2X and/or metabotropic P2Y receptors. Chemosensors located in the brainstem are crucial for the maintenance of physiological levels of blood gases through the regulation of breathing(9-11). Here we show that an increase in p(CO 2) in the arterial blood triggers the immediate release of ATP from three chemosensitive regions located on the ventral surface of the medulla oblongata. Blockade of ATP receptors at these sites diminishes the chemosensory control of breathing, suggesting that ATP release constitutes a key step in central chemosensory transduction. These new data suggest that ATP, a phylogenetically ancient, unique and simple molecule, has been widely used in the evolution of afferent systems to mediate distinct forms of sensory transduction not only in the periphery but also within the central nervous system.