Magnani M, Bianchi M, Rossi L, Stocchi V
Istituto di Chimica Biologica, Università degli Studi, Urbino, Italy.
Biochem Int. 1989 Aug;19(2):227-34.
The mechanism by which 2,3'-dideoxycytidine, an inhibitor of HIV-I infectivity, permeates the cell membrane was investigated. The influx of ddCyd into human erythrocytes was nonconcentrative. The initial velocity of both ddCyd influx and efflux was, in contrast to compounds that permeate the cell membrane via the nucleoside transporter, a linear function of nucleoside concentration in the 1 microM to 10 mM range and relatively insensitive to temperature. Furthermore, potent inhibitors of nucleoside transporter and other nucleosides were found to inhibit ddCyd influx only partially or not at all suggesting that ddCyd permeates the human erythrocyte membrane predominantly by nonfacilitated diffusion. This unusual characteristic seems to be due to the lack of 3'-hydroxyl moiety of ddCyd which appears to be an important determinant for the nucleoside carrier specificity rather than to lipid solubility itself. As far as permeation of the cell membrane is concerned ddCyd shares these properties with 2',3'-dideoxythymidine and 3'-azido-3'-deoxythymidine.
对HIV-I感染性抑制剂2,3'-二脱氧胞苷透过细胞膜的机制进行了研究。ddCyd进入人红细胞的过程是非浓缩性的。与通过核苷转运体透过细胞膜的化合物不同，ddCyd流入和流出的初始速度在1微摩尔至10毫摩尔范围内是核苷浓度的线性函数，且对温度相对不敏感。此外，发现核苷转运体的强效抑制剂和其他核苷仅部分抑制或根本不抑制ddCyd的流入，这表明ddCyd主要通过非易化扩散透过人红细胞膜。这种不寻常的特性似乎是由于ddCyd缺乏3'-羟基部分，这似乎是核苷载体特异性的一个重要决定因素，而不是脂质溶解度本身。就细胞膜的渗透而言，ddCyd与2',3'-二脱氧胸苷和3'-叠氮-3'-脱氧胸苷具有这些共同特性。
