Nerbonne J M, Richard S, Nargeot J, Lester H A
Nature. 1984;310(5972):74-6. doi: 10.1038/310074a0.
The cyclic nucleotides cyclic AMP and cyclic GMP are important intracellular messengers mediating the responses to neurotransmitters and neurohormones and regulating cellular function over a wide range of time scales. Despite the widespread acceptance of this second messenger mechanism in many systems, much remains unknown about their mechanism of action, except that such events are associated with increases or decreases in intracellular cyclic nucleotides. Quantitative descriptions of cyclic nucleotide-dependent processes are hampered by the absence of a means by which intracellular cyclic nucleotide concentrations can be accurately controlled. We have now designed, synthesized and characterized new, substituted photolabile cyclic nucleotide analogues, the 4,5-dimethoxy-2-nitrobenzyl esters of cyclic AMP and cyclic GMP (Fig. 1), which are physiologically inert before irradiation and which liberate free cyclic AMP or cyclic GMP on absorption of a photon. The thermal properties and photolysis rates and efficiencies of light-induced release of cyclic nucleotides from these analogues are more favourable than for the simple o-nitrobenzyl derivatives used previously. These molecules should permit intracellular "concentration jumps' of cyclic AMP or cyclic GMP to be produced in cells under physiological investigation with spatial and temporal resolution unmatched by conventional techniques.
环核苷酸环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）是重要的细胞内信使，介导对神经递质和神经激素的反应，并在广泛的时间尺度上调节细胞功能。尽管这种第二信使机制在许多系统中已被广泛接受，但除了这些事件与细胞内环核苷酸的增加或减少有关外，它们的作用机制仍有许多未知之处。由于缺乏准确控制细胞内环核苷酸浓度的方法，对环核苷酸依赖性过程的定量描述受到了阻碍。我们现已设计、合成并表征了新的、经取代的光不稳定环核苷酸类似物，即cAMP和cGMP的4,5-二甲氧基-2-硝基苄酯（图1），它们在照射前是生理惰性的，在吸收光子后会释放出游离的cAMP或cGMP。这些类似物的热性质、光解速率以及光诱导释放环核苷酸的效率比以前使用的简单邻硝基苄基衍生物更有利。这些分子应能使在生理研究中的细胞产生cAMP或cGMP的细胞内“浓度跃升”，其空间和时间分辨率是传统技术无法比拟的。
