Analysis of drug transport kinetics in multidrug-resistant cells using a novel coumarin-vinblastine compound.
Analysis of drug transport kinetics in multidrug-resistant cells using a novel coumarin-vinblastine compound.
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使用新型香豆素-长春花碱化合物分析多重耐药细胞中的药物转运动力学。
DOI：
10.1021/bi00208a018
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
P. Roepe
中科院分区：
文献类型：
--
作者：
W. Bornmann;P. Roepe
We have synthesized an analogue of vinblastine wherein a coumarin molecule is attached to the C17 of the vindoline moiety via a succinimide bridge (cou-VBL). cou-VBL exhibits fluorescence similar to that exhibited by coumarin. Chinese hamster ovary fibroblasts (LR73 cells) that exhibit an IC50 for vinblastine (VBL) of about 100 nM in growth inhibition assays are similarly sensitive to the cou-VBL compound. LR73 cells transfected with the mu MDR 3 gene that were subsequently selected on vinblastine (MDR35 cells) exhibit resistance to cou-VBL that is similar to their VBL resistance. A large change in the quantum efficiency of cou-VBL fluorescence accompanies efflux from intact cells, and comparison between cou-VBL and [3H]VBL efflux from the MDR35 cells reveals that the transport kinetics of the fluorescent analogue is very similar (if not identical) to that exhibited by [3H]VBL. Thus, similar to continuous monitoring of fluorescence (CMF) studies performed with the naturally fluorescent chemotherapeutic doxorubicin (Roepe, 1992), cou-VBL may be used in CMF studies aimed at rigorously defining the kinetics of VBL efflux from multidrug-resistant (MDR) cells. Initial data suggest the following: (1) A single exponential term approximates efflux from sensitive cells, whereas two exponentials are required to fit efflux from MDR35 cells. (2) The faster MDR35 term is virtually identical to the single term for the sensitive cells, whereas the other defines a process that is 5-20 times slower than passive diffusion, depending on the drug concentration. (3) The slower component has a much steeper and nearly linear dependence on drug concentration, whereas the fast passive diffusion component becomes asymptotic near 0.3 pM exchangeable drug/microgram of cell protein.
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DOI：
10.1016/0304-4157(89)90008-7
发表时间：
1989-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
O. Eidelman;Z. Cabantchik
通讯作者：
O. Eidelman;Z. Cabantchik
影响因子：
2.9
作者：
PROCHASKA, HJ;SANTAMARIA, AB
通讯作者：
SANTAMARIA, AB
能量依赖性药物结合减少是人类白血病淋巴母细胞长春花生物碱耐药的机制。
影响因子：
3.6
作者：
Beck,WT;Cirtain,MC;Lefko,JL
通讯作者：
Lefko,JL
DOI：
10.1073/pnas.85.19.7187
发表时间：
1988-10-01
影响因子：
11.1
作者：
SAFA, AR
通讯作者：
SAFA, AR
酿酒酵母中甘氨酸-质子共转运的动力学和 pH 依赖性。
DOI：
10.1016/0005-2736(84)90442-5
发表时间：
1984
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ballarin-Denti,A;DenHollander,JA;Sanders,D;Slayman,CW;Slayman,CL
通讯作者：
Slayman,CL