Sarkadi B, Müller M, Homolya L, Holló Z, Seprödi J, Germann U A, Gottesman M M, Price E M, Boucher R C
National Institute of Haematology, Blood Transfusion and Immunology, Budapest, Hungary.
FASEB J. 1994 Jul;8(10):766-70. doi: 10.1096/fasebj.8.10.7914178.
In this report we demonstrate that various biologically active hydrophobic peptide derivatives, e.g., proteinase inhibitors, chemoattractants, ionophores, enkephalins, and immunosuppressants, stimulate a membrane ATPase activity associated with the human multidrug transporter (MDR1). The stimulation of the MDR1-ATPase by these agents does not correlate with their known biochemical or pharmacological activities but rather with their hydrophobicity. The peptides that show high-affinity interaction with the MDR1-ATPase also interfere strongly with fluorescent dye extrusion catalyzed by the multidrug transporter in intact cells and some have been shown to reverse drug resistance in cultured cells. These data suggest that several hydrophobic peptides behave as substrates of the multidrug transporter and may be used to modulate the chemotherapy resistance of tumor cells.
在本报告中，我们证明了各种生物活性疏水肽衍生物，例如蛋白酶抑制剂、趋化因子、离子载体、脑啡肽和免疫抑制剂，可刺激与人多药转运蛋白（MDR1）相关的膜ATP酶活性。这些试剂对MDR1-ATP酶的刺激与其已知的生化或药理活性无关，而是与其疏水性有关。与MDR1-ATP酶表现出高亲和力相互作用的肽也强烈干扰完整细胞中多药转运蛋白催化的荧光染料外排，并且一些已被证明可逆转培养细胞中的耐药性。这些数据表明，几种疏水肽可作为多药转运蛋白的底物，并可用于调节肿瘤细胞的化疗耐药性。
