Santos Ricardo M, Lourenço Cátia F, Ledo Ana, Barbosa Rui M, Laranjinha João
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Int J Cell Biol. 2012;2012:391914. doi: 10.1155/2012/391914. Epub 2012 Jun 10.
During the last decades nitric oxide ((•)NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain. (•)NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how (•)NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamics in vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological (•)NO concentration and what constitutes a pathological one and how is (•)NO concentration regulated. The ambient (•)NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of (•)NO synthesis, but the inactivation pathways of (•)NO has been almost completely ignored. We have recently addressed these issues in vivo on basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement (•)NO concentration dynamics in the brain.
在过去几十年中，一氧化氮（•NO）已成为哺乳动物组织尤其是大脑中的一种关键生理信号分子。•NO可通过与血红素部分直接反应，或通过硫醇基团的S-亚硝基化或酪氨酸残基的硝化间接改变调节蛋白的活性。然而，由于缺乏对其体内动力学的了解，对•NO在生物系统中的生物活性如何发挥作用仍缺乏概念性认识。仍然缺乏具体明确答案的关键问题包括与其浓度动态和扩散的定量问题相关的问题，总结为“多少、多久、多远”三部曲。例如，一个主要问题是缺乏对什么构成生理•NO浓度、什么构成病理浓度以及•NO浓度如何调节的了解。环境•NO浓度反映了合成速率和分解速率之间的平衡。关于•NO合成机制已经了解很多，但•NO的失活途径几乎完全被忽视。我们最近基于微电极技术在体内解决了这些问题，该技术允许对大脑中•NO浓度动态进行微调的空间和时间测量。
