Forray M I, Angelo S, Boyd C A, Devés R
Department of Physiology and Biophysics, Faculty of Medicine, University of Chile, Santiago, Chile.
Biochem Pharmacol. 1995 Dec 22;50(12):1963-8. doi: 10.1016/0006-2952(95)02090-x.
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.
研究了已知可抑制一氧化氮合酶的精氨酸类似物与人红细胞的两种阳离子氨基酸转运体（y+系统和y+L系统）之间的相互作用。发现精氨酸及相关类似物[NG-单甲基-L-精氨酸（L-NMMA）；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红细胞。正如预期的那样，抑制模式反映了两种不同转运系统的作用。所有类似物对y+L系统的亲和力均高于对y+系统的亲和力。y+系统和y+L系统的半饱和（抑制）常数（±标准误）（微摩尔）分别为：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。使用基于赖氨酸流出反刺激的测定方法研究了类似物的转运特性。向外部介质中添加饱和浓度的未标记类似物可刺激标记的赖氨酸通过y+L系统和y+系统流出，表明类似物可通过这些途径进入细胞。
