Renal elimination of p-aminohippurate (PAH) in response to three days of biliary obstruction in the rat. The role of OAT1 and OAT3

被引:45
作者
Brandoni, Anabel
Anzai, Naohiko
Kanai, Yoshikatsu
Endou, Hitoshi
Torres, Adriana Monica
机构
[1] Univ Nacl Rosario, CONICET, Fac Ciencias Bioquim & Farmaceut, RA-2000 Rosario, Santa Fe, Argentina
[2] Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2006年 / 1762卷 / 07期
基金
日本学术振兴会;
关键词
p-aminohippurate; cholestasis; renal depuration; OAT1; OAT3;
D O I
10.1016/j.bbadis.2006.05.011
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
Pharmacokinetic studies of the drugs administered to subjects with mechanical cholestasis are scarce. The purpose of the present study was to examine the effects of bile duct ligation of 3 days (peak of elevation of serum bile acids and bilirubin) on the systemic and. renal PAH clearance and on the expression of cortical renal OAT1 and OAT3 in a rat model. PAH is the prototypical substrate of the renal organic anion transport system. Male Wistar rats underwent a bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. BDL rats displayed a significantly lower systemic PAH clearance. Renal studies revealed a reduction in the renal clearance and in the excreted and secreted load of PAH in BDL rats. The OAT1 protein expression in kidney homogenates was not modified, but it decreased in the basolateral membranes from BDL rats. In contrast, OAT3 abundance in both kidney cortex homogenates and in basolateral membranes increased by 3 days after the ligation. Immunocytochemical studies (light microscopic and confocal immunofluorescence microscopic analyses) confirmed the changes in the renal expression of these transport proteins. The present study demonstrates the key role of OAT1 expression in the impaired elimination of PAH after 3 days of obstructive cholestasis. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:673 / 682
页数:10
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