Different efflux rates may determine the cellular accumulation of various bis(guanylhydrazones).
Different efflux rates may determine the cellular accumulation of various bis(guanylhydrazones).
复制标题
不同的流出速率可以决定各种双(脒基腙)的细胞积累。
作者：
L. Alhonen;R. Fagerström;R. Laine;H. Elo;J. Jänne
比较了三种双胍腙（甲基乙二醛、乙二醛和乙基乙二醛）对假定的多胺载体的亲和力和它们在L1210小鼠白血病细胞中的细胞保留。所有的双胍腙都同样有效地抑制肿瘤细胞对亚精胺的摄取，这表明这些化合物对多胺载体的亲和力大致相同。甲基乙二醛二（鸟酰腙）和乙二醛二（鸟酰腙）在动物细胞内的富集效率远高于乙基乙二醛二（鸟酰腙），这显然是由于发现乙基乙二醛二（鸟酰腙）的外排速率大大超过其他两种乙二醛二（鸟酰腙）。如果肿瘤细胞在暴露于双胍腙之前先用2-二氟甲基鸟氨酸处理，则药物外流的速度会减慢。这些结果表明，双胍腙在细胞内的结合决定了它们在细胞内的积累。
Three bis(guanylhydrazones) (those of methylglyoxal, glyoxal and ethylglyoxal) were compared for their affinity for the putative polyamine carrier and for their cellular retention in L1210 mouse leukaemia cells. All the bis(guanylhydrazones) inhibited equally effectively the uptake of spermidine by the tumour cells, indicating that the compounds had roughly equal affinity for the polyamine carrier. The fact that methylglyoxal bis(guanylhydrazone) and glyoxal bis(guanylhydrazone) were much more effectively concentrated in the animal cells than was ethylglyoxal bis(guanylhydrazone) was obviously attributable to the finding that the efflux rate of ethylglyoxal bis(guanylhydrazone) greatly exceeded that of the other bis(guanylhydrazones). The rate of efflux of the drugs was slowed down if the tumour cells were treated with 2-difluoromethylornithine before exposure to the bis(guanylhydrazones). These results suggest that intracellular binding of the bis(guanylhydrazones) determines their cellular accumulation.