Role of rat multidrug resistance protein 2 in plasma and biliary disposition of dibromosulfophthalein after microsomal enzyme induction

Toxicology and Applied Pharmacology
David R Johnson, C D Klaassen

Abstract

We have previously demonstrated that microsomal enzyme inducers phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN), but not 3-methylcholanthrene (3-MC) and benzo(a)pyrene (BaP), increase expression and function of rat Multidrug Resistance Protein 2 (Mrp2), a canalicular organic anion transporter. Thus, the purpose of this study was to determine whether Mrp2 protein induction alters the biliary and plasma dispositions of dibromosulfophthalein (DBSP). After four daily ip injections of PB, PCN, 3-MC, BaP, or vehicle, DBSP (100 mg/kg) was injected iv and was measured in blood and bile over a 40-min period. PB and PCN significantly enhanced plasma disappearance and biliary excretion of DBSP, whereas 3-MC and BaP did not. To determine whether the enhanced plasma disappearance and biliary excretion was entirely due an increase in Mrp2, PCN was also administered ip daily for 4 days to Mrp2-null Eisai hyperbilirubinemic (EHBR) rats and then injected iv with DBSP. PCN significantly increased plasma DBSP disappearance in EHBR rats during early time intervals (2-20 min), but not at later time intervals (25-40 min). PCN did not increase DBSP biliary excretion in EHBR rats, but actually decreased it at later time intervals. In su...Continue Reading

References

Jan 1, 1987·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P L JansenD F Meijer
Jul 1, 1985·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P L JansenW H Lamers
Aug 1, 1997·Journal of the American Society of Nephrology : JASN·T P SchaubD Keppler
Jun 8, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L C Rausch-DerraC D Klaassen
Feb 28, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·David R JohnsonCurtis D Klaassen

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Citations

Feb 28, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Scott A ReismanCurtis D Klaassen
Nov 17, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Katie B PaulKevin M Crofton
May 21, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chuan ChenJose E Manautou

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