Swelling-activated chloride currents in a drug-sensitive cell line and a P glycoprotein-expressing derivative are underlied by channels with the same pharmacological properties
Swelling-activated chloride currents in a drug-sensitive cell line and a P glycoprotein-expressing derivative are underlied by channels with the same pharmacological properties
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DOI：
10.1159/000016287
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发表时间：
1998-01-01
影响因子：
--
通讯作者：
Reuss, L
中科院分区：
文献类型：
--
作者：
Horton, JK;Vanoye, CG;Reuss, L
已有研究表明，P糖蛋白（Pgp）的表达与多药耐药细胞中肿胀激活的Cl-电流有关。Pgp底物长春碱和调节剂维拉帕米在药物敏感细胞系（MCF-7）和表达Pgp的衍生物（BC 19/3）中产生了可逆的浓度依赖性肿胀激活Cl-电流阻断，在两种细胞系中获得的结果的相似性表明，阻断机制与Pgp表达无关，并支持Pgp表达对于阻断是不必要的这一假设。Cl-电流的膨胀激活。与长春碱的结果相反，其他两种细胞骨架破坏剂，秋水仙碱和细胞松弛素D，不能影响任何一种细胞系中的溶胀激活的Cl-电流，这些数据提供了Ilo证据，表明细胞骨架参与了这些细胞系中Cl-通道的溶胀激活。氯离子通道阻断剂，5-硝基-2-（3-苯基丙基氨基）苯甲酸和4，4 ′-二异硫氰基芪-2，2 ′-二磺酸，各自在Pgp表达和非表达细胞中的溶胀激活电流中产生类似的可逆的浓度依赖性阻断。这强烈地表明，在两种细胞系中负责溶胀依赖性电流的Cl-通道是相同的，由于MCF-7细胞不表达Pgp，因此Pgp不是这些细胞中负责体积激活Cl-电流通道。
It has been proposed that P glycoprotein (Pgp) expression is associated with swelling-activated Cl- currents in multidrug-resistant cells. The Pgp substrate vinblastine and the modulator verapamil produced a reversible concentration-dependent block of swelling-activated Cl- currents in both a drug-sensitive cell line (MCF-7) and a Pgp-expressing derivative (BC19/3), The similarity of the results obtained in both cell lines suggests that the mechanism of block is not related to Pgp expression and supports the hypothesis that Pgp expression is not necessary for the swelling activation of Cl- currents. In contrast to the results obtained with vinblastine, two other cytoskeleton-disrupting agents, colchicine and cytochalasin D, were not able to affect the swelling-activated Cl- currents in either cell line, The data provided Ilo evidence for the involvement of the cytoskeleton in the swelling activation of Cl- channels in these cell lines. The Cl- channel blockers, 5-nitro-2-(3-phenylpropylamino)benzoic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, each produced a similar reversible concentration-dependent block in the swelling-activated currents in both the Pgp-expressing and nonexpressing cells, This strongly suggests that the Cl- channel(s) responsible for the swelling-dependent current in both cell lines are the same and, since MCF-7 cells do not express Pgp, that Pgp is not the channel responsible for the volume-activated Cl- currents in these cells.