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Citations to this article

Hepatobiliary transport of glutathione and glutathione conjugate in rats with hereditary hyperbilirubinemia.
R P Elferink, … , J de Haan, P L Jansen
R P Elferink, … , J de Haan, P L Jansen
Published August 1, 1989
Citation Information: J Clin Invest. 1989;84(2):476-483. https://doi.org/10.1172/JCI114189.
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Hepatobiliary transport of glutathione and glutathione conjugate in rats with hereditary hyperbilirubinemia.

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Abstract

TR- mutant rats have an autosomal recessive mutation that is expressed as a severely impaired hepatobiliary secretion of organic anions like bilirubin-(di)glucuronide and dibromosulphthalein (DBSP). In this paper, the hepatobiliary transport of glutathione and a glutathione conjugate was studied in normal Wistar rats and TR- rats. It was shown that glutathione is virtually absent from the bile of TR- rats. In the isolated, perfused liver the secretion of glutathione and the glutathione conjugate, dinitrophenyl-glutathione (GS-DNP), from hepatocyte to bile is severely impaired, whereas the sinusoidal secretion from liver to blood is not affected. The secretion of GS-DNP was also studied in isolated hepatocytes. The secretion of GS-DNP from cells isolated from TR- rat liver was significantly slower than from normal hepatocytes. Efflux of GS-DNP was a saturable process with respect to intracellular GS-DNP concentration: Vmax and Km for efflux from TR- cells was 498 nmol/min.g dry wt and 3.3 mM, respectively, as compared with 1514 nmol/min.g dry wt and 0.92 mM in normal hepatocytes. These results suggest that the canalicular transport system for glutathione and glutathione conjugates is severely impaired in TR- rats, whereas sinusoidal efflux is unaffected. Because the defect also comes to expression in isolated hepatocytes, efflux of GS-DNP from normal hepatocytes must predominantly be mediated by the canalicular transport mechanism, which is deficient in TR- rats.

Authors

R P Elferink, R Ottenhoff, W Liefting, J de Haan, P L Jansen

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The Journal of biological chemistry 1992
ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles
Y Adachi, H Kobayashi, Y Kurumi, M Shouji, M Kitano, T Yamamoto
Hepatology 1991
Glutathione metabolism and its role in hepatotoxicity
LD DeLeve, N Kaplowitz
Pharmacology & Therapeutics 1991
Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant sprague-dawley rat
H Takikawa, N Sano, T Narita, Y Uchida, M Yamanaka, T Horie, T Mikami, O Tagaya
Hepatology 1991
Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid transport system
T Nishida, Z Gatmaitan, M Che, IM Arias
Proceedings of the National Academy of Sciences 1991
Inhibition of glutathione-conjugate secretion from isolated hepatocytes by dipolar bile acids and other organic anions
RP Elferink, R Ottenhoff, A Radominska, AF Hofmann, F Kuipers, PL Jansen
Biochemical Journal 1991
Hepatocanalicular organic-anion transport is regulated by protein kinase C
H Roelofsen, R Ottenhoff, RP Elferink, PL Jansen
Biochemical Journal 1991
The anionic conjugates of bilirubin and bile acids stimulate ATP hydrolysis by S-(dinitrophenyl)glutathione ATPase of human erythrocyte
SS Singhal, R Sharma, S Gupta, H Ahmad, P Zimniak, A Radominska, R Lester, YC Awasthi
FEBS Letters 1991
Purification and characterization of an ATPase from human liver which catalyzes ATP hydrolysis in the presence of the conjugates of bilirubin, bile acids and glutathione
YC Awasthi, SS Singhal, S Gupta, H Ahmad, P Zimniak, A Radominska, R Lester, R Sharma
Biochemical and Biophysical Research Communications 1991
ATP-Dependent transport for glucuronides in canalicular plasma membrane vesicles
K Kobayashi, S Komatsu, T Nishi, H Hara, K Hayashi
Biochemical and Biophysical Research Communications 1991
New insights into canalicular organic anion secretion
RH Moseley
Hepatology 1991
Liver Pathology and Alcohol
RR Watson
1991
ATP-dependent S-(2,4-dinitrophenyl)glutathione transport in canalicular plasma membrane vesicles from rat liver
TP Akerboom, V Narayanaswami, M Kunst, H Sies
The Journal of biological chemistry 1991
Intrahepatic conversion of a glutathione conjugate to its mercapturic acid. Metabolism of 1-chloro-2,4-dinitrobenzene in isolated perfused rat and guinea pig livers
CA Hinchman, H Matsumoto, TW Simmons, N Ballatori
The Journal of biological chemistry 1991
Defective ATP-dependent bile canalicular transport of organic anions in mutant (TR-) rats with conjugated hyperbilirubinemia
T Kitamura, P Jansen, C Hardenbrook, Y Kamimoto, Z Gatmaitan, IM Arias
Proceedings of the National Academy of Sciences 1990
The uncoupling of biliary lipid from bile acid secretion by organic anions in the rat
HJ Verkade, MJ Wolbers, R Havinga, DR Uges, RJ Vonk, F Kuipers
Gastroenterology 1990
Mechanism of glutathione S-conjugate transport in canalicular and basolateral rat liver plasma membranes
K Kobayashi, Y Sogame, H Hara, K Hayashi
The Journal of biological chemistry 1990
Cellular Mechanisms of Intrahepatic Cholestasis:
PJ Meier-Abt
Drugs 1990
Evidence for leukotriene C4 transport mediated by an ATP-dependent glutathione S-conjugate carrier in rat heart and liver plasma membranes
T Ishikawa, K Kobayashi, Y Sogame, K Hayashi
FEBS Letters 1989

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