2010 年 35 巻 6 号 p. 297-304
Transport characteristics of ribavirin in human erythrocytes were evaluated using rightside-out membrane vesicles (ROVs) prepared from fresh blood, and compared with those in intact erythrocytes. [3H]Ribavirin uptake by ROVs at 23 °C was fairly rapid, and reached equilibrium at about 30 sec. The uptake of [3H]ribavirin by ROVs showed saturation kinetics with the Km value of 1.9 mM. The uptake by ROVs was inhibited by uridine (a typical substrate of equilibrative nucleoside transporter ENT1), S-(4-nitrobenzyl)-6-thioinosine (a specific inhibitor of ENT1), and dipyridamole (an inhibitor of ENT1). These characteristics of [3H]ribavirin transport in ROVs were similar to those observed in intact erythrocytes, though the affinity of [3H]ribavirin to the transport system and sensitivity to various inhibitors were lower in ROVs. Next, the interaction of ribavirin with ATP-dependent efflux transporters was evaluated using inside-out membrane vesicles (IOVs). Ribavirin weakly inhibited ATP-dependent uptake of methotrexate by multidrug resistance-associated protein (MRP) 4, but not the uptake of 5-(and 6)-carboxy-2', 7'-dichlorofluorescein by MRP5, by IOVs. However, ATP-dependent uptake of [3H]ribavirin by IOVs was not observed. These results suggest that ribavirin is transported by ENT1 across human erythrocyte membranes, while ATP-dependent efflux transporters would not be involved in ribavirin transport.
