MODELS OF THE DIFFUSIONAL SPREAD OF NITRIC-OXIDE - IMPLICATIONS FOR NEURAL NITRIC-OXIDE SIGNALING AND ITS PHARMACOLOGICAL PROPERTIES
MODELS OF THE DIFFUSIONAL SPREAD OF NITRIC-OXIDE - IMPLICATIONS FOR NEURAL NITRIC-OXIDE SIGNALING AND ITS PHARMACOLOGICAL PROPERTIES
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DOI：
10.1016/0028-3908(94)90022-1
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发表时间：
1994-11-01
影响因子：
4.7
通讯作者：
GARTHWAITE, J
中科院分区：
文献类型：
--
作者：
WOOD, J;GARTHWAITE, J
一氧化氮（NO）在包括大脑在内的许多不同组织中充当可扩散的使者分子。为了创建一个概念框架，以理解生物学（尤其是神经生物学）情景中NO的行为，我们开发了理论的模型，描述了单个或多个来源产生的NO的动力学和浓度曲线。据预测，发射1-10秒的单点源的生理范围的直径约为200 mu m，对应于封闭200万突触的大脑量。由于扩散如此之快，因此NO（以0.5-5秒为单位的半衰期为0.5-5秒）的灭活仅具有相对较小的影响。当组织体积内有多个同时活跃的无源源，并且在没有衰减的情况下或源强度的时间依赖性降低的情况下，NO的浓度仅随时间线性而线性上升，表明可能有负反馈的重要性没有合成。远处的来源（200-500 mu m远）即使在NO的半衰期是岸边（0.5-5秒），在这种情况下稳态的NO浓度也有很大的贡献。这些模型预测了几个被解释为表明不含分子的药理实验的结果，而不是本身是内源性信使。因此，没有必要根据这些实验结果来调用假设的“无载体”。
Nitric oxide (NO) functions as a diffusible messenger molecule in many different tissues, including the brain. To create a conceptual framework for understanding the behaviour of NO in a biological (particularly neurobiological) scenario, we have developed theoretical,models describing the kinetic and concentration profiles for NO generated from single or multiple sources. It is predicted that the physiological sphere of influence of a single point source of NO that emits for 1-10 sec has a diameter of about 200 mu m, corresponding to a volume of brain enclosing 2 million synapses. Inactivation of NO (imposed as a half-life of 0.5-5 sec) has only relatively minor effects because diffusion is so fast. When there are multiple simultaneously-active NO sources within a tissue volume, and in the absence of decay of NO or of a time-dependent reduction in source strength, the concentration of NO simply rises linearly with time, indicating the likely importance of negative feedback by NO on NO synthesis. Distant sources (200-500 mu m away) make significant contributions to the steady-state NO concentrations in this situation even when the half-life of NO is shore (0.5-5 sec). The models predict the results of several pharmacological experiments that were interpreted to suggest that a NO-containing molecule, rather than NO itself is the endogenous messenger. Accordingly, invoking the presence of a hypothetical ''NO carrier'' on the basis of these experimental results is unnecessary.