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Real-time measurement of adenosine and ATP release in the central nervous system
Purinergic Signalling ( IF 3.5 ) Pub Date : 2020-10-06 , DOI: 10.1007/s11302-020-09733-y
Nicholas Dale 1
Affiliation  

This brief review recounts how, stimulated by the work of Geoff Burnstock, I developed biosensors that allowed direct real-time measurement of ATP and adenosine during neural function. The initial impetus to create an adenosine biosensor came from trying to understand how ATP and adenosine-modulated motor pattern generation in the frog embryo spinal cord. Early biosensor measurements demonstrated slow accumulation of adenosine during motor activity. Subsequent application of these biosensors characterized real-time release of adenosine in in vitro models of brain ischaemia, and this line of work has recently led to clinical measurements of whole blood purine levels in patients undergoing carotid artery surgery or stroke. In parallel, the wish to understand the role of ATP signalling in the chemosensory regulation of breathing stimulated the development of ATP biosensors. This revealed that release of ATP from the chemosensory areas of the medulla oblongata preceded adaptive changes in breathing, triggered adaptive changes in breathing via activation of P2 receptors, and ultimately led to the discovery of connexin26 as a channel that mediates CO2-gated release of ATP from cells.



中文翻译:

中枢神经系统腺苷和ATP释放的实时测量

这篇简短的评论讲述了我如何在 Geoff Burnstock 工作的激励下开发出生物传感器,允许在神经功能期间直接实时测量 ATP 和腺苷。创建腺苷生物传感器的最初动力来自试图了解青蛙胚胎脊髓中 ATP 和腺苷调节运动模式的生成。早期的生物传感器测量表明运动活动期间腺苷的积累缓慢。这些生物传感器的后续应用表征了脑缺血体外模型中腺苷的实时释放,并且这项工作最近导致了对接受颈动脉手术或中风的患者的全血嘌呤水平的临床测量。在平行下,了解 ATP 信号在呼吸化学感应调节中的作用的愿望刺激了 ATP 生物传感器的发展。这表明延髓化学感应区释放的 ATP 先于呼吸的适应性变化,通过激活 P2 受体触发呼吸的适应性变化,并最终导致发现连接蛋白 26 作为介导 CO 的通道ATP 从细胞中的2 门控释放。

更新日期:2020-10-07
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