Lambert L E, Whitten J P, Baron B M, Cheng H C, Doherty N S, McDonald I A
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Life Sci. 1991;48(1):69-75. doi: 10.1016/0024-3205(91)90426-c.
Inhibition of nitric oxide production by arginine analogues was examined in three cell systems; macrophages, CNS tissue and endothelial cells. Nitric oxide production was assessed indirectly using in vitro assays measuring nitrite production (macrophages), cGMP elevation (CNS) and acetylcholine-induced relaxation of aortic ring segments (endothelium). NG-monomethyl-L-arginine and NG-amino-L-arginine possessed similar inhibitory activity in all three assays, while NG-nitro-L-arginine displayed a striking selectivity for inhibition of brain and endothelial cell nitric oxide synthesis, with IC50 values of 0.05 microM in the CNS versus 200 microM in macrophages. These results suggest that distinct enzymes are responsible for nitric oxide synthesis in different cell types, and indicate that it may be possible to selectively modulate nitric oxide production in vivo.
在三种细胞体系（巨噬细胞、中枢神经系统组织和内皮细胞）中研究了精氨酸类似物对一氧化氮生成的抑制作用。使用体外测定法间接评估一氧化氮生成，这些测定法分别测量亚硝酸盐生成（巨噬细胞）、环鸟苷酸升高（中枢神经系统）以及乙酰胆碱诱导的主动脉环段舒张（内皮）。在所有这三种测定中，NG-单甲基-L-精氨酸和NG-氨基-L-精氨酸具有相似的抑制活性，而NG-硝基-L-精氨酸对脑和内皮细胞一氧化氮合成的抑制表现出显著的选择性，中枢神经系统中的IC50值为0.05微摩尔，而巨噬细胞中的IC50值为200微摩尔。这些结果表明，不同的酶负责不同细胞类型中的一氧化氮合成，并表明在体内选择性调节一氧化氮生成可能是可行的。
