The interaction of arginine analogues, which are known to inhibit nitric oxide synthase, with two cationic amino acid transporters of human erythrocytes (systems y+ and y+L) was studied. Arginine and relevant analogues [NG-monomethyl-L-arginine (L-NMMA); NG-monomethyl-D-arginine (D-NMMA) and NG-nitro-L-arginine (L-NOARG)] were found to inhibit labeled lysine influx into intact erythrocytes. As expected, the pattern of inhibition reflected the contribution of the two distinct transport systems. All analogues showed a higher affinity for system y+L than for system y+. The half-saturation (inhibition) constants estimated for systems y+ and y+L (+/- SEM) were (microM)L-arginine, 55.7 +/- 5.4 and 2.4 +/- 0.1; L-NMMA, 151 +/- 13 and 7.5 +/- 0.5; D-NMMA, 2660 +/- 404 and 269 +/- 25; L-NOARG, 9414 +/- 169 and 594 +/- 35. The transport properties of the analogues were investigated using an assay based on the trans-stimulation of lysine efflux. The addition of saturating concentrations of unlabeled analogues to the external medium stimulated efflux of labeled lysine through systems y+L and y+, showing that the analogues can enter the cell through these pathways.

译文

研究了已知能抑制一氧化氮合酶的精氨酸类似物与人类红细胞的两种阳离子氨基酸转运蛋白(系统y和y L)的相互作用。精氨酸和相关类似物[NG-单甲基-L-精氨酸(L-NMMA);发现NG-单甲基-D-精氨酸(D-NMMA)和NG-硝基-L-精氨酸(L-NOARG)]可抑制标记的赖氨酸流入完整的红细胞。不出所料,抑制模式反映了两种不同运输系统的贡献。所有类似物对系统y L的亲和力均高于对系统y的亲和力。对于系统y和y L(/ -SEM)估计的半饱和(抑制)常数为(microM)L-精氨酸,55.7 / -5.4和2.4 / -0.1; L-NMMA,151 /-13和7.5 /-0.5; D-NMMA,2660 /-404和269 /-25; L-NOARG,9414 /-169和594 /-35。使用基于赖氨酸外排的反式刺激的分析方法研究了类似物的转运特性。将饱和浓度的未标记类似物添加到外部介质中会刺激标记的赖氨酸通过系统y L和y流出,这表明类似物可以通过这些途径进入细胞。

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