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

页码：2822 / 2831

页数：10

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