Huang Z H, Murakami T, Okochi A, Yumoto R, Nagai J, Takano M
Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Eur J Pharmacol. 2000 Oct 20;406(3):453-60. doi: 10.1016/s0014-2999(00)00699-3.
The effect of glycerol-induced acute renal failure on P-glycoprotein expression and function was evaluated in rats. The in vivo function of P-glycoprotein was evaluated by measuring renal secretory and biliary clearance and brain distribution of rhodamine 123 (Rho-123), a P-glycoprotein substrate, under a steady-state plasma concentration. In acute renal failure rats, the P-glycoprotein level increased 2.5-fold in the kidney, but not in the liver and brain. In contrast, P-glycoprotein function in these tissues was suppressed. Interestingly, not only the renal but also the biliary clearance of Rho-123 was correlated with the glomerular filtration rate. In Caco-2 cells, plasma from renal failure rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of Rho-123 than did plasma from control rats. In conclusion, P-glycoprotein function was systemically suppressed in acute renal failure, even though the level of P-glycoprotein remained unchanged or rather increased. This may be due to the accumulation of some endogenous P-glycoprotein substrates/modulators in the plasma in disease states.
在大鼠中评估了甘油诱导的急性肾衰竭对P-糖蛋白表达和功能的影响。通过在稳态血浆浓度下测量P-糖蛋白底物罗丹明123（Rho-123）的肾脏分泌、胆汁清除率及脑部分布，评估P-糖蛋白的体内功能。在急性肾衰竭大鼠中，肾脏中P-糖蛋白水平增加了2.5倍，但肝脏和脑中未增加。相反，这些组织中的P-糖蛋白功能受到抑制。有趣的是，Rho-123的肾脏清除率和胆汁清除率均与肾小球滤过率相关。在Caco-2细胞中，肾衰竭大鼠的血浆对P-糖蛋白介导的Rho-123转运的抑制作用比对照大鼠的血浆更强。总之，在急性肾衰竭中，P-糖蛋白功能受到全身抑制，尽管P-糖蛋白水平保持不变或反而升高。这可能是由于疾病状态下血浆中一些内源性P-糖蛋白底物/调节剂的积累所致。
