Ding G Y, Shen T, Center M S
Division of Biology, Kansas State University, Manhattan 66506, USA.
Anticancer Res. 1999 Jul-Aug;19(4B):3243-8.
Studies have been carried out to examine in vitro drug transport in plasma membrane vesicles isolated from HL60/ADR cells that overexpress MRP. The results demonstrate that glutathione (GSH) enhances transport of daunomycin. A greater increase in transport activity occurs when the reaction is carried out in the presence of both GSH and sodium chloride. Sodium chloride alone has no effect on daunomycin transport. It has also been observed that GSH in the presence of sodium chloride induces a major increase in the transport level of LTC4. Thus far, no metal ion other than sodium chloride has been found to be active in the drug transport system. Kinetic analysis reveals that GSH in the presence of sodium chloride greatly reduces Km and increases Vmax, for daunomycin. Additional studies show that ATPase activity in isolated plasma membrane from HL60/ADR cells is greatly enhanced in the presence of both GSH and sodium chloride. These results suggest the possibility that GSH and sodium chloride stimulate MRP-mediated transport as a result of increased ATPase activity.
已有研究对从过表达多药耐药相关蛋白（MRP）的HL60/ADR细胞中分离出的质膜囊泡进行体外药物转运检测。结果表明，谷胱甘肽（GSH）可增强柔红霉素的转运。当反应在GSH和氯化钠同时存在的情况下进行时，转运活性有更大程度的增加。单独的氯化钠对柔红霉素转运没有影响。还观察到，在氯化钠存在的情况下，GSH可诱导白三烯C4（LTC4）转运水平大幅增加。到目前为止，尚未发现除氯化钠以外的其他金属离子在药物转运系统中具有活性。动力学分析表明，在氯化钠存在的情况下，GSH可大大降低柔红霉素的米氏常数（Km）并提高最大反应速度（Vmax）。进一步的研究表明，在GSH和氯化钠同时存在的情况下，HL60/ADR细胞分离出的质膜中的ATP酶活性大大增强。这些结果提示，GSH和氯化钠可能由于ATP酶活性增加而刺激MRP介导的转运。
