INTERACTION OF P-GLYCOPROTEIN WITH A HYDROPHOBIC COMPONENT OF RAT URINE

被引:16
作者
CHARUK, JHM [1 ]
REITHMEIER, RAF [1 ]
机构
[1] UNIV TORONTO,DEPT BIOCHEM,TORONTO M5S 1A8,ONTARIO,CANADA
关键词
D O I
10.1016/0006-291X(92)90816-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The presence of an endogenous P-glycoprotein substrate in rat urine was examined by testing the ability of a hydrophobic extract to reverse multidrug resistance in CHO cells and to inhibit [3H]azidopine photolabelling. The accumulation of several hydrophobic drugs and dyes, known to be transported by P-glycoprotein, was dramatically enhanced in multidrug-resistant CHO cells (CHRC5) by a component contained in a hydrophobic extract prepared from rat urine by octadecyl (C18) reverse phase chromatography. The biological action of this urinary component involves a direct interaction with P-glycoprotein since it blocked photolabelling of the protein with [3H]azidopine. The effective concentration of the substance required to enhance drug accumulation and inhibit photolabelling was similar and within the range of its urinary content. These results suggest that a hydrophobic substance in urine may be an endogenous substrate of kidney P-glycoprotein. © 1992.
引用
收藏
页码:796 / 802
页数:7
相关论文
共 18 条
  • [1] CARMICHAEL J, 1987, CANCER RES, V47, P936
  • [2] FOJO A, 1985, CANCER RES, V45, P3002
  • [3] FOXWELL BMJ, 1989, MOL PHARMACOL, V36, P543
  • [4] REDUCED CYCLOSPORIN ACCUMULATION IN MULTIDRUG-RESISTANT CELLS
    GOLDBERG, H
    LING, V
    WONG, PY
    SKORECKI, K
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 152 (02) : 552 - 558
  • [5] GOTTESMAN MM, 1991, MOL CELLULAR BIOL MU, P279
  • [6] HORIO M, 1989, J BIOL CHEM, V264, P14880
  • [7] MODULATORS OF THE MULTIDRUG TRANSPORTER, P-GLYCOPROTEIN, EXIST IN THE HUMAN-PLASMA
    ICHIKAWA, M
    YOSHIMURA, A
    FURUKAWA, T
    SUMIZAWA, T
    AKIYAMA, S
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 166 (01) : 74 - 80
  • [8] ICHIKAWA M, 1991, J BIOL CHEM, V266, P903
  • [9] SURFACE GLYCOPROTEIN MODULATING DRUG PERMEABILITY IN CHINESE-HAMSTER OVARY CELL MUTANTS
    JULIANO, RL
    LING, V
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1976, 455 (01) : 152 - 162
  • [10] DETECTION OF P-GLYCOPROTEIN IN MULTIDRUG-RESISTANT CELL-LINES BY MONOCLONAL-ANTIBODIES
    KARTNER, N
    EVERNDENPORELLE, D
    BRADLEY, G
    LING, V
    [J]. NATURE, 1985, 316 (6031) : 820 - 823