Vetrovsky P, Kleschyov A L, Entlicher G, Poindron P, Stoclet J C
Laboratoire de Pharmacologie et de Physiopathologie Cellulaires-CNRS URA600, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Illkirch, France.
Biochim Biophys Acta. 1997 Feb 11;1334(1):51-6. doi: 10.1016/s0304-4165(96)00074-8.
Lipopolysaccharide (LPS)-activated but not control RAW 264 macrophages produced nitric oxide (NO) from extracellularly-applied NG-hydroxy-L-arginine (L-NOHA) in a concentration-dependent manner, as measured by EPR spin trapping and assays for NO2- and NO3-. This production was inhibited by NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, NO-synthase inhibitors, as well as by L-lysine, a competitor for the y+ amino acid carrier system. No significant differences were found between L-NOHA and L-arginine with respect to the rate of NO production and the effects of inhibitors. These results provide evidence that extracellular L-NOHA can enter LPS-activated RAW 264 macrophages via a cationic amino acid carrier system and be metabolized to NO by NO-synthase. The data also suggest that no alternative pathway exists for NO production from L-NOHA in non-activated RAW 264 macrophages.
脂多糖（LPS）激活而非对照的RAW 264巨噬细胞以浓度依赖的方式从细胞外施加的Nω-羟基-L-精氨酸（L-NOHA）产生一氧化氮（NO），通过电子顺磁共振自旋捕获以及NO2-和NO3-测定法进行测量。这种产生受到Nω-硝基-L-精氨酸甲酯和Nω-单甲基-L-精氨酸（NO合酶抑制剂）以及L-赖氨酸（一种阳离子氨基酸载体系统的竞争剂）的抑制。在NO产生速率和抑制剂作用方面，L-NOHA和L-精氨酸之间未发现显著差异。这些结果提供了证据，表明细胞外L-NOHA可通过阳离子氨基酸载体系统进入LPS激活的RAW 264巨噬细胞，并被NO合酶代谢为NO。数据还表明，在未激活的RAW 264巨噬细胞中，不存在L-NOHA产生NO的替代途径。
