Cyclosporin A treatment induces overexpression of P-glycoprotein in the kidney and other tissues

被引:84
作者
Jette, L
Beaulieu, E
Leclerc, JM
Beliveau, R
机构
[1] UNIV QUEBEC, DEPT CHIM BIOCHIM, MOLEC ONCOL LAB, MONTREAL, PQ H3C 3P8, CANADA
[2] HOP ST JUSTINE, MONTREAL, PQ H3T 1C5, CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY | 1996年 / 270卷 / 05期
关键词
renal brush-border membranes; multidrug resistance; protein expression;
D O I
10.1152/ajprenal.1996.270.5.F756
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
To see whether P-glycoprotein (PGP) expressed in renal brush-border membranes (BBM) could interact with compounds known as modulators of multidrug resistance (MDR), photoaffinity-labeling experiments were performed. A. 145-kDa protein was photolabeled with [I-125]iodoarylazidoprazosin, and this labeling was reduced in the presence of cyclosporin A (CsA) and PSC-833 (PSC). Interaction of CsA with PGP was fur ther investigated by treating rats with daily subcutaneous injections of CsA (10 mg . kg(-1). day(-1)). After this treatment, PGP expression levels were dramatically increased in renal BBM, intestine, liver, and many other tissues except the brain. This induction was a reversible process, since after cessation of CsA administration PGP levels declined to reach values similar to those of the control groups. The increase in PGP expression in the kidney was also detected in photolabeling experiments, suggesting the induction of a functional PGP. A higher dose of CsA (50 mg/kg) given as a bolus injection did not modify PGP expression in renal BBM. These results demonstrate that CsA induces reversible overexpression of PGP in the rat. This may present significant relevance in the design of clinical trials using CsA as a chemosensitizing agent.
引用
收藏
页码:F756 / F765
页数:10
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