Hepatic, intestinal and renal transport of 1-naphthol-β-d-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia

Vries, M. Hugo de; Redegeld, Frank A.; Koster, Andries S.; Noordhoek, J.; Haan, J; Elferink, Ronald P.J. Oude; Jansen, Petér L. M.

doi:10.1007/bf00260615

Cited by 43 publications

(36 citation statements)

References 11 publications

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“…These results render it likely that the transporter in Caco-2 cells is different from that in the hepatocanalicular membrane. The latter conclusion is in line with observations by de Vries et al [26] on the intestinal secretion of naphthylglucuronide in normal and TR-rats. The TR-rat has a hereditary defect in the above described cMOAT.…”

Section: Discussionsupporting

confidence: 93%

“…The TR-rat has a hereditary defect in the above described cMOAT. Organic anions like GS-DNP and naphthyl-glucuronide are not secreted into the bile of these rats [20,26]. De Vries et al [26] have administered 1-naphthol to the isolated perfused rat small intestine; they demonstrated that glucuronide of 1-naphthol is secreted at both the luminal and the vascular side.…”

Section: Discussionmentioning

confidence: 98%

“…Organic anions like GS-DNP and naphthyl-glucuronide are not secreted into the bile of these rats [20,26]. De Vries et al [26] have administered 1-naphthol to the isolated perfused rat small intestine; they demonstrated that glucuronide of 1-naphthol is secreted at both the luminal and the vascular side. They also found that in the TR-rat this secretion is unaffected indicating that glucuronide secretion in small intestine and canalicular membrane of the liver indeed involves different organ-specific gene products.…”

Section: Discussionmentioning

confidence: 98%

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Glutathione-conjugate transport by human colon adenocarcinoma cells (Caco-2 cells)

Elferink

Bakker

Jansen

1993

Biochemical Journal

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The secretion of a glutathione-S-conjugate, dinitrophenyl-glutathione (GS-DNP) was studied in the Caco-2 cells, a cultured human colonic adenocarcinoma cell line with many of the characteristics of enterocytes. The labelled glutathione conjugate was generated within the cell by incubation with 14C-labelled 1-chloro-2,4-dinitrobenzene (CDNB). This compound is hydrophobic and enters the cell by simple diffusion. Cells incubated with CDNB at 10 degrees C form only one metabolite, GS-DNP. After secretion into the medium GS-DNP is partly converted into one or two slightly more hydrophobic products. This must represent hydrolysis of the glutathione moiety by the action of gamma-glutamyltransferase (EC 2.3.2.2.; gamma-GT) because the reaction was completely inhibited by acivicin, an inhibitor of gamma-GT. Secretion of GS-DNP was a temperature-sensitive, saturable process with an apparent Km of 1.03 +/- 0.26 nmol/mg of protein and a Vmax of 111 +/- 17 pmol/min per mg of protein. The secretion was not sensitive to trans-stimulation by extracellular concentrations of GS-DNP up to 2.5 mM. Furthermore the initial GS-DNP secretion rate was sensitive to dissipation of the membrane potential and correlated closely with the cellular ATP content. Caco-2 cells cultured on nitrocellulose filters secreted GS-DNP significantly faster over the basolateral membrane than over the apical membrane (146 +/- 25 versus 90 +/- 18 pmol/min per mg respectively). Secretion over both membrane domains of the cell was sensitive to ATP depletion. In conclusion, Caco-2 cells contain an active-transport system that is primarily involved in the secretion of glutathione conjugates and that is present in both plasma membrane domains of the cell.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Glutathione-conjugate transport by human colon adenocarcinoma cells (Caco-2 cells)

Elferink

Bakker

Jansen

1993

Biochemical Journal

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“…Furthermore, the genetic defect in TR -/GY rats is specific for liver since no impaired organic anion transport activi- [51] ty is observed in the intestine or kidney of these rats [47]. Other, organ-specific, transport systems are apparently involved in the intestinal and renal clearance of organic anions.…”

Section: Hepatobiliary Transport Of Bile Salt and Nonbile Salt Organimentioning

confidence: 97%

“…Secondly, Evers et al [66] demonstrated that the hMRP1 protein is routed predominantly to the lateral domain of the basolateral membrane when transfected into the (polarized) epithilial pig kidney cell line LLC-PK1, which renders it unlikely that hMRP1 is responsible for the hepatobiliary (apical) excretion of organic anions. Thirdly, and most importantly, the transport defect in the TR -/GY rat appears to be specific for the liver [47], wheras hMRP1 is expressed in all human tissues [65].…”

Section: Isolation Of the Rat Cmoat Cdnamentioning

confidence: 99%

The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man

Paulusma

Elferink

1997

Journal of Molecular Medicine

104

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The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man Paulusma, C.C.; Oude Elferink, R.P.J. Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 22 Mar 2019& p . 1 : Abstract The human Dubin-Johnson syndrome is an autosomal recessive liver disease characterized by a chronic conjugated hyperbilirubinemia. Patients have impaired hepatobiliary transport of many endogenous and xenobiotic compounds. A similar disease phenotype has been described for a naturally occurring mutant Wistar rat strain, the TR -rat, which is defective in the, functionally defined, canalicular multispecific organic anion transporter (cMOAT). The complementary DNA encoding this protein has been cloned from rat and recently from human liver. cMOAT is a new member of the ATPbinding cassette transporter family, and homologous to the multidrug resistance-associated protein 1. A mutation in the cMOAT gene is responsible for the phenotype observed in TR -rats. This information should soon lead to a complete genetic characterization of the human DubinJohnson syndrome.

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ATP-dependent transport systems for organic anions

Zimniak

Awasthi

1993

Hepatology

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Hepatic, intestinal and renal transport of 1-naphthol-β-d-glucuronide in mutant rats with hereditary-conjugated hyperbilirubinemia

Cited by 43 publications

References 11 publications

Glutathione-conjugate transport by human colon adenocarcinoma cells (Caco-2 cells)

Glutathione-conjugate transport by human colon adenocarcinoma cells (Caco-2 cells)

The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man

ATP-dependent transport systems for organic anions

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