A unique multifunctional transporter translocates estradiol-17beta -glucuronide in rat liver microsomal vesicles

The Journal of Biological Chemistry
E Battaglia, J L Gollan

Abstract

A wide array of drugs, xenobiotics, and endogenous compounds undergo detoxification by conjugation with glucuronic acid in the liver via the action of UDP-glucuronosyltransferases. The mechanism whereby glucuronides, generated by this enzyme system in the lumen of the endoplasmic reticulum (ER), are exported to the cytosol prior to excretion is unknown. We examined this process in purified rat liver microsomes using a rapid filtration technique and [(3)H]estradiol-17beta-d-glucuronide ([(3)H]E(2)17betaG) as model substrate. Time-dependent uptake of intact [(3)H]E(2)17betaG was observed and shrinkage of ER vesicles by raffinose lowered the steady-state level of [(3)H]E(2)17betaG accumulation. In addition, rapid efflux of [(3)H]E(2)17betaG from rat liver microsomal vesicles suggested that the transport process is bidirectional. Microsomal uptake was saturable with an apparent K(m) and V(max) of 3.29 +/- 0.58 microm and 0.19 +/- 0.02 nmol.min(-1).mg protein(-1), respectively. Transport of [(3)H]E(2)17betaG was inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and probenecid. Specificity of the transport process was investigated by studying the cis-inhibitory effect of anionic metabolite...Continue Reading

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Citations

Feb 24, 2007·The International Journal of Biochemistry & Cell Biology·Katalin RévészMiklós Csala
Sep 4, 2004·Biochemical Pharmacology·Miklós CsalaBrian Burchell
Apr 4, 2006·FEBS Letters·Miklós CsalaAngelo Benedetti
Mar 19, 2003·Journal of Neurochemistry·Kuresh A YoudimCatherine Rice-Evans
Apr 14, 2006·American Journal of Physiology. Cell Physiology·Beáta LizákGábor Bánhegyi
Apr 29, 2004·The American Journal of Clinical Nutrition·Claudine ManachLiliana Jiménez
May 1, 2007·Biochimica Et Biophysica Acta·Miklós CsalaGábor Bánhegyi

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