Pou S J, Anderson D E, Surichamorn W, Keaton L L, Tod M L
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
Mol Pharmacol. 1994 Oct;46(4):709-15.
2-Methyl-2-nitrosopropane (MNP) has long been known to undergo photochemical and thermal decomposition, generating di-tert-butyl nitroxide, in organic solvent. The present study was undertaken to demonstrate that MNP can be used as a caged-nitric oxide (NO), which can liberate NO upon illumination. Photolysis of MNP leads to the generation of tert-butyl radical and NO, as detected by spin-trapping/ESR spectroscopy and by oxyhemoglobin/visible spectroscopy, respectively. Using soluble guanylate cyclase in neuroblastoma N1E-115 cells as an NO target, we found that MNP in the presence of light caused a dose- and time-dependent increase in cGMP. Finally, illumination of a solution of MNP was also found to induce relaxation of preconstricted isolated rat pulmonary artery rings. These studies demonstrated that MNP can be useful biochemical research tool for delivering NO in a controlled manner, by using light.
长期以来,人们已知2-甲基-2-亚硝基丙烷(MNP)在有机溶剂中会发生光化学和热分解,生成二叔丁基氮氧化物。本研究旨在证明MNP可作为一种笼形一氧化氮(NO),在光照下能够释放出NO。通过自旋捕获/电子顺磁共振光谱法和氧合血红蛋白/可见光谱法分别检测发现,MNP的光解会导致叔丁基自由基和NO的生成。以神经母细胞瘤N1E-115细胞中的可溶性鸟苷酸环化酶作为NO作用靶点,我们发现光照条件下的MNP会使环磷酸鸟苷(cGMP)呈剂量和时间依赖性增加。最后,还发现照射MNP溶液可诱导预先收缩的离体大鼠肺动脉环舒张。这些研究表明,通过光照,MNP可以作为一种有用的生化研究工具,以可控方式递送NO。