Apparent differences in mechanisms of harmol sulfate biliary excretion in mice and rats.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Maciej J Zamek-GliszczynskiKim L R Brouwer

Abstract

Previous experiments demonstrated that the biliary excretion of harmol sulfate (HS) was mediated by breast cancer resistance protein (Bcrp) and not by multidrug resistance-associated protein (Mrp)2 or P-glycoprotein in mice. However, recent reports suggested that species differences in hepatic canalicular transport mechanisms for a given substrate exist between mice and rats. In the present study, biliary excretion of HS was examined in perfused livers from mice and rats in the absence or presence of the P-glycoprotein and Bcrp inhibitor N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918). As expected, in mouse liver perfusions, the biliary excretion of HS was decreased approximately 3.5-fold by GF120918, consistent with previous reports of Bcrp-mediated HS biliary excretion. However, despite sufficient hepatic unbound concentrations of GF120918 to achieve extensive inhibition of Bcrp, the biliary excretion of HS was not decreased significantly in wild-type (50 +/- 12 versus 41 +/- 6%) or TR(-) (18 +/- 2 versus 16 +/- 3%) Wistar rats. In summary, biliary excretion of HS was mediated by a GF120918-sensitive mechanism in mice, previously elucidate...Continue Reading

References

Jun 1, 1994·Chemico-biological Interactions·K S PangM Chiba
Apr 19, 2003·The Journal of Biological Chemistry·Michiko SuzukiYuichi Sugiyama
May 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Noam ZelcerPiet Borst
Feb 14, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Maciej J Zamek-GliszczynskiKim L R Brouwer
Jul 22, 2006·The Journal of Pharmacology and Experimental Therapeutics·Maciej J Zamek-GliszczynskiKim L R Brouwer

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Citations

Nov 26, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wei YueKim L R Brouwer
Mar 8, 2017·Drug Metabolism Reviews·Guangyi YangMing Hu
May 7, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kyunghee Yang, Kim L R Brouwer
Jun 29, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Maciej J Zamek-GliszczynskiDiane L Phillips

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