Heijn M, Oude Elferink R P, Jansen P L
Division of Gastrointestinal and Liver Diseases, Academic Medical Centre, Amsterdam, The Netherlands.
Am J Physiol. 1992 Jan;262(1 Pt 1):C104-10. doi: 10.1152/ajpcell.1992.262.1.C104.
The uptake of oxidized glutathione (GSSG) into inside-out membrane vesicles of Wistar rat erythrocytes was studied. Uptake was ATP dependent, into an osmotically active space, and saturable. Analysis of saturable ATP-dependent GSSG uptake showed two affinities for GSSG [concentration for half-maximal velocity (K1/2 1), 26 microM; K 1/2 2, 4 mM; maximum transport rate (Vmax 1), 100 pmol.mg-1.min-1; Vmax 2, 360 pmol.mg-1.min-1]. Interactions of the high-affinity system with different organic compounds were studied. Leukotriene C4, bromosulfophthalein-S-glutathione, and 2,4-dinitrophenyl-S-glutathione were effective inhibitors. In addition, anionic nonglutathione conjugates, like indocyanine green, rose bengal, dibromosulfophthalein, and sulfated or glucuronidated (divalent) bile acids inhibited GSSG transport. Monovalent bile acids had no influence on GSSG transport. Inhibition by 2,4-dinitrophenyl-S-glutathione [inhibition constant (Ki) = 2.6 microM] and sulfated glycolithocholic acid (Ki = 2.9 microM) was purely competitive. The use of adenosinetriphosphatase (ATPase) inhibitors suggested a resemblance with E1E2-type ATPase. Vesicles of erythrocytes isolated from the TR- rat, a mutant rat strain with a defective biliary secretion of organic anions, have an impaired uptake of GSSG (Vmax was decreased 2-fold). In conclusion, erythrocytes have an ATP-dependent organic anion transport system that can be inhibited by a broad range of organic anions. This system is very similar if not identical to the hepatocanalicular ATP-dependent organic anion transporter.
研究了氧化型谷胱甘肽（GSSG）进入Wistar大鼠红细胞内翻膜囊泡的过程。摄取过程依赖ATP，进入渗透活性空间，且具有饱和性。对依赖ATP的GSSG饱和摄取分析显示，其对GSSG有两种亲和力[半数最大速度时的浓度（K1/2 1），26 μM；K1/2 2，4 mM；最大转运速率（Vmax 1），100 pmol·mg-1·min-1；Vmax 2，360 pmol·mg-1·min-1]。研究了高亲和力系统与不同有机化合物的相互作用。白三烯C4、溴磺酞谷胱甘肽和2,4-二硝基苯谷胱甘肽是有效的抑制剂。此外，阴离子非谷胱甘肽共轭物，如吲哚菁绿、孟加拉玫瑰红、二溴磺酞和硫酸化或葡萄糖醛酸化（二价）胆汁酸可抑制GSSG转运。单价胆汁酸对GSSG转运无影响。2,4-二硝基苯谷胱甘肽[抑制常数（Ki）= 2.6 μM]和硫酸化甘氨石胆酸（Ki = 2.9 μM）的抑制作用完全是竞争性的。使用腺苷三磷酸酶（ATPase）抑制剂表明其与E1E2型ATPase相似。从TR-大鼠（一种有机阴离子胆汁分泌有缺陷的突变大鼠品系）分离的红细胞囊泡对GSSG的摄取受损（Vmax降低了2倍）。总之，红细胞具有依赖ATP的有机阴离子转运系统，该系统可被多种有机阴离子抑制。该系统即使不完全相同，也与肝小管依赖ATP的有机阴离子转运体非常相似。
