Effect of Ursodeoxycholic Acid Treatment on the Expression and Function of Multidrug Resistance-Associated Protein 2 in Rat Intestine

被引：6
作者：
Yumoto, Ryoko [1 ]
Hamada, Shota [1 ]
Okada, Kaori [1 ]
Kato, Yuki [1 ]
Ikehata, Mika [1 ]
Nagai, Junya [1 ]
Takano, Mikihisa [1 ]
机构：
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pharmaceut & Therapeut, Minami Ku, Hiroshima 7348553, Japan
来源：
JOURNAL OF PHARMACEUTICAL SCIENCES | 2009年 / 98卷 / 08期
关键词：
UDCA; Mrp2; DNP-SG; methotrexate; intestine; ACUTE HEPATIC-FAILURE; P-GLYCOPROTEIN SUBSTRATE; LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; BILE-ACIDS; 3A-RELATED COMPOUNDS; EFFLUX TRANSPORTERS; MOUSE-LIVER; ABSORPTION; CYTOCHROME-P450;
D O I：
10.1002/jps.21628
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Effect of ursodeoxycholic acid (UDCA) treatment on the expression and function of intestinal multidrug resistance-associated protein (Mrp) 2 was examined in rats. When rats were orally administered 0.5% UDCA solution for 6 days, mRNA and protein levels of Mrp2 in the intestine were increased about twofold compared with those in untreated rats. In in vitro everted sac study, Mrp2-mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-SG) to the mucosal surface was shown to be increased by UDCA treatment. In vivo intestinal exsorption clearance of DNP-SG was also increased by UDCA treatment. In addition, in situ intestinal absorption of methotrexate, a substrate of Mrp2, was decreased by the treatment. These results indicate that the expression and function of intestinal Mrp2 is up-regulated by oral administration of UDCA. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2822-2831, 2009
引用
收藏
页码：2822 / 2831
页数：10
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