Excretion multidrug resistant proteins

Smeets PH, van Auhel RA, Wouterse AC, et al. Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 2004 15 2828-2835. 

It has been suggested that multidrug resistance proteins (MRPs) play an important role in the transport and detoxification of a wide range of endogenous compounds and xenobiotics. They are predominantly expressed at the apical membrane of the small intestine, proximal tubules of the kidney and canalicular membrane of hepatocytes involved in intestinal, renal and hepatobiliary excretion of compounds. 

Jager, W., Gehring, E., Hagenauer, B.,Aust, S., Senderowicz, A., and Thalhammer, T. (2003) Bihary excretion of flavopiridol and its glucuronides in fhe isolated pei fiised rat liven role of multidrug resistance protein 2 (Mrp2). Life Sciences, 17, 2841-2854. 

Slitt, A. L., Cherrington, N. J., Maher, J. M., and Klaassen, C. D. (2003) Induction of multidrug resistance protein 3 in rat liver is associated with altered vectorial excretion of acetaminophen metabolites. Drug Metab. Dispos. 31, 1176-1186. 

Biliary Excretion Mediated by Multidrug Resistance-Associated Protein 2 (MRP2)... 

Zamek-GI i szczy nski MJ, Nezasa K, Tian X, et al. Evaluation of the role of multidrug resistance-associated protein (Mrp) 3 and Mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in Abcc3-/- and Abcc4-/- mice. J Pharmacol Exp Ther 2006 319 1485-1491. 

Hasegawa M, Kusuhara H, Adachi M, et al. Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol 2007 18 37 15. 

Lohitnavy M, Lu Y, Lohitnavy O, Chubb LS, Hirono S, Yang RSH. 2008. A possible role of multidrug resistance-associated protein 2 (Mrp2) in hepatic excretion of PCB126, an environmental contaminant PBPK/PD modeling. Toxicol Sci 104 27-39. 

Tian, X., Zamek-Gliszczynski, M.J., Li, J., Bridges, A.S., Nezasa, K., Patel, N.J., Raub, T.J. and Brouwer, K.L. (2008) Multidrug resistance-associated protein 2 is primarily responsible for the biliary excretion of fexofenadine in mice. Drug Metabolism and Disposition The Biological Fate of Chemicals, 36, 61-64. 

The water soluble conjugate is finally eliminated from the cell by transport proteins (organic anion transporters, multidrug resistance associated proteins), and finally excreted via the renal or the bile route. This transport step is considered as phase HI of drug metabolism. It does not require further biotransformation, and will be not considered in this chapter. 

Sulforaphane has also been shown to attenuate the induction of DNA strand breaks by N-nitrosodimethylamine (NDMA) and 2-amino-3-methylimidazo[4,5f]quinoxaline (IQ) in T-antigen-immortalized human liver cells [96]. Moreover, sulforaphane induces levels of multidrug resistance-associated protein 2 (MRP2), an efflux pump contributing to biliary secretion of xenobiotics [97]. MRP2 protects against PhiP by biliary excretion of the parent compound and all major phase II metabolites [98, 99]. Furthermore, in two... 

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