What is the real physiological NO concentration in vivo?
What is the real physiological NO concentration in vivo?
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DOI：
10.1016/j.niox.2009.07.002
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Garthwaite J
中科院分区：
文献类型：
--
作者：
Hall CN;Garthwaite J
明确生理状态下存在的一氧化氮（NO）浓度对于定量理解NO信号传导、进行模拟现实的NO实验以及了解疾病状态下NO浓度是否异常至关重要。十年前，基于早期的电极测量以及对NO与其鸟苷酸环化酶偶联受体（介导生理NO信号转导）亲和力的初步估计，约1μM的值似乎是合理的。从那时起，许多在细胞和组织中直接使用电极测量NO浓度的尝试得出了差异极大且无法调和的值。作为弥补，来自几种替代方法的数据现在已经趋于一致，提供了更连贯的图像。这些方法包括对NO激活的鸟苷酸环化酶的定量分析、基于细胞中所含NO合酶的类型、活性和数量的计算机建模、使用新型生物传感器监测单个内皮细胞和神经元的NO释放，以及在受到各种刺激的组织中使用鸟苷酸环化酶作为内源性NO生物传感器。所有这些独立的证据都表明，生理NO浓度范围为100 pM（或更低）至约5 nM，比曾经认为的低几个数量级。
Clarity about the nitric oxide (NO) concentrations existing physiologically is essential for developing a quantitative understanding of NO signalling, for performing experiments with NO that emulate reality, and for knowing whether or not NO concentrations become abnormal in disease states. A decade ago, a value of about 1 μM seemed reasonable based on early electrode measurements and a provisional estimate of the potency of NO for its guanylyl cyclase-coupled receptors, which mediate physiological NO signal transduction. Since then, numerous efforts to measure NO concentrations directly using electrodes in cells and tissues have yielded an irreconcilably large spread of values. In compensation, data from several alternative approaches have now converged to provide a more coherent picture. These approaches include the quantitative analysis of NO-activated guanylyl cyclase, computer modelling based on the type, activity and amount of NO synthase enzyme contained in cells, the use of novel biosensors to monitor NO release from single endothelial cells and neurones, and the use of guanylyl cyclase as an endogenous NO biosensor in tissue subjected to a variety of challenges. All these independent lines of evidence suggest the physiological NO concentration range to be 100 pM (or below) up to ∼5 nM, orders of magnitude lower than was once thought.
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