Comparative studies on the transport of aminopterin, methotrexate, and methasquin by the L1210 leukemia cell.
Comparative studies on the transport of aminopterin, methotrexate, and methasquin by the L1210 leukemia cell.
复制标题
L1210 白血病细胞转运氨基蝶呤、甲氨蝶呤和甲沙喹的比较研究。
作者：
F. Sirotnak;R. C. Donsbach
比较了氨蝶呤、甲氨蝶呤和喹唑啉类抗叶酸药物甲喹喹在L1210白血病细胞中的摄取情况。用细菌二氢叶酸还原酶滴定法测定细胞内药物含量。这三种药物都是通过载体介导的转运进入细胞的，因为摄取是依赖于温度的、饱和的和集中的。在这三种药物中，氨基蝶呤的运输效率最高。在相同的限速外部浓度下，甲氨蝶呤的转运效率是氨蝶呤的四分之一，甲喹的转运效率是氨蝶呤的二十分之一。三种药物运输能力的差异，如初始摄取速度的Michaelis常数所示，似乎与每种药物的载体成分亲和力的差异有关。这三种药物似乎通过相同的机制运输，因为这三种药物之间以及它们与正常类似物叶酸和亚叶酸酸盐之间对同一载体成分的竞争被证明具有预期的定量关系。氨蝶呤和甲氨蝶呤从L1210细胞流出的速率远远大于甲喹的速率。氨蝶呤在内流（摄取）期间的集中摄取程度略高于甲氨蝶呤或甲喹在内流限速浓度下的集中摄取程度。
Comparison was made of the uptake in L1210 leukemia cells of the agents aminopterin, methotrexate, and the quinazoline antifolate methasquin. Intracellular drug content was measured by titration with a bacterial dihydrofolate reductase. All three agents gain entry into the cell by carrier-mediated transport, since uptake is temperature dependent, saturable, and concentrative. Of the three drugs, aminopterin is transported most efficiently. At the same rate-limiting external concentration, the transport of methotrexate is one-fourth as efficient as that of aminopterin and the transport of methasquin is one-twentieth as efficient. Differences in the ability of the three drugs to be transported, as indicated by the respective Michaelis constants for initial uptake velocity, seem related to a difference in the affinity of a carrier component for each drug. All three drugs appear to be transported by the same mechanism, since competition for the same carrier component among the three drugs, as well as between them and the normal analogs, folate and folinate, was demonstrated with the expected quantitative relationships. The rate of efflux of aminopterin and methotrexate from the L1210 cell is far greater than the rate for methasquin. The extent of concentrative uptake during influx (uptake) of aminopterin is somewhat higher than that for methotrexate or methasquin at a rate-limiting concentration for influx.