Einzeltreffer — DigiBib

Purpose: The mechanism for the biliary excretion of 17beta-estradiol 17beta-D-glucuronide (E(2)17betaG), a cholestatic metabolite of estradiol, is still controversial. The purpose of the present study is to examine the transport of E(2)17betaG across the bile canalicular membrane.

Methods: We examined the uptake of [3H]E(2)17betaG by isolated canalicular membrane vesicles (CMVs) prepared from Sprague-Dawley (SD) rats and Eisai Hyperbilirubinemic rats (EHBR) whose canalicular multispecific organic anion transporter/multidrug resistance associated protein 2 (cMOAT/MRP2) function is hereditarily defective. Also, in vivo biliary excretion of intravenously administered [3H]E(2)17betaG was examined.

Results: In CMVs prepared from SD rats, but not from EHBR, a marked ATP-dependent uptake of [3H]E(2)17betaG was observed. Moreover, E(2)17betaG competitively inhibited the ATP-dependent uptake of [3H]2,4-dinitrophenyl-S-glutathione (DNP-SG). In addition, no significant inhibitory effect of verapamil (100 microM) and PSC-833 (5 microM) on the uptake of [3H]E(2)17betaG was observed. In vivo, the biliary excretion of intravenously administered [3H]E(2)17betaG was severely impaired in EHBR while the biliary excretion of [3H]E(2)17betaG in SD rats was reduced by administering a cholestatic dose (10 micromol/kg) unlabeled E(2)17betaG, but not by PSC-833 (3 mg/kg).

Conclusions: The transport of E(2)17betaG across the bile canalicular membrane is predominantly mediated by cMOAT/MRP2.

Titel:	Biliary excretion of 17beta-estradiol 17beta-D-glucuronide is predominantly mediated by cMOAT/MRP2.
Autor/in / Beteiligte Person:	Morikawa, A ; Goto, Y ; Suzuki, H ; Hirohashi, T ; Sugiyama, Y
Link:	Full Text Finder (Volltext)
Zeitschrift:	Pharmaceutical research, Jg. 17 (2000-05-01), Heft 5, S. 546-52
Veröffentlichung:	1999- : New York, NY : Kluwer Academic/Plenum Publishers ; <i>Original Publication</i>: Stuttgart ; New York : Thieme, c1984-, 2000
Medientyp:	academicJournal
ISSN:	0724-8741 (print)
DOI:	10.1023/a:1026412915168
Schlagwort:	Animals Anion Transport Proteins Bile Canaliculi metabolism Carrier Proteins genetics Cell Membrane metabolism Chromatography, Thin Layer Estradiol pharmacokinetics Glutathione analogs & derivatives Glutathione metabolism Hyperbilirubinemia genetics Hyperbilirubinemia metabolism Injections, Intravenous Male Rats Rats, Sprague-Dawley Bile metabolism Carrier Proteins metabolism Estradiol analogs & derivatives
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Pharm Res] 2000 May; Vol. 17 (5), pp. 546-52. MeSH Terms: Bile / metabolism ; Carrier Proteins / metabolism ; Estradiol / *analogs & derivatives ; Animals ; Anion Transport Proteins ; Bile Canaliculi / metabolism ; Carrier Proteins / genetics ; Cell Membrane / metabolism ; Chromatography, Thin Layer ; Estradiol / pharmacokinetics ; Glutathione / analogs & derivatives ; Glutathione / metabolism ; Hyperbilirubinemia / genetics ; Hyperbilirubinemia / metabolism ; Injections, Intravenous ; Male ; Rats ; Rats, Sprague-Dawley References: Biochim Biophys Acta. 1995 Jul 17;1241(2):215-68. (PMID: 7640297) ; J Biol Chem. 1990 May 15;265(14):7737-41. (PMID: 2335503) ; Hepatology. 1999 Apr;29(4):1156-63. (PMID: 10094960) ; Drug Metab Rev. 1997 Feb-May;29(1-2):183-203. (PMID: 9187518) ; Biol Pharm Bull. 1998 Aug;21(8):874-8. (PMID: 9743261) ; J Biol Chem. 1999 May 21;274(21):15181-5. (PMID: 10329726) ; J Pharmacol Exp Ther. 1997 Aug;282(2):866-72. (PMID: 9262353) ; Hepatology. 1998 Nov;28(5):1371-7. (PMID: 9794924) ; Am J Physiol. 1996 Nov;271(5 Pt 1):G791-8. (PMID: 8944692) ; Curr Opin Cell Biol. 1998 Aug;10(4):462-7. (PMID: 9719866) ; Proc Natl Acad Sci U S A. 1999 Jun 8;96(12 ):6914-9. (PMID: 10359813) ; Mol Pharmacol. 1998 Jun;53(6):1068-75. (PMID: 9614210) ; J Biol Chem. 1989 Jul 15;264(20):11693-8. (PMID: 2568355) ; Gastroenterology. 2000 Feb;118(2):422-30. (PMID: 10648470) ; Drug Metab Dispos. 1999 Jun;27(6):689-94. (PMID: 10348798) ; Gastroenterology. 1997 Jul;113(1):255-64. (PMID: 9207286) ; Biochem Pharmacol. 1996 Oct 11;52(7):967-77. (PMID: 8831715) ; J Biol Chem. 1998 Jun 26;273(26):16184-91. (PMID: 9632674) ; J Pharmacol Exp Ther. 1999 Feb;288(2):627-34. (PMID: 9918568) ; Am J Physiol. 1997 Jan;272(1 Pt 1):G16-22. (PMID: 9038871) ; J Clin Invest. 1993 Jun;91(6):2714-20. (PMID: 8514879) ; Semin Liver Dis. 1998;18(4):359-76. (PMID: 9875554) ; Eur J Cancer. 1996 Jun;32A(6):945-57. (PMID: 8763335) ; Hepatology. 1996 Mar;23(3):607-13. (PMID: 8617443) ; J Pharm Sci. 1998 Sep;87(9):1025-40. (PMID: 9724551) ; J Biol Chem. 1996 Jun 21;271(25):15091-8. (PMID: 8662992) ; FEBS Lett. 1993 Oct 25;333(1-2):193-6. (PMID: 8224162) ; Hepatology. 1998 Feb;27(2):537-45. (PMID: 9462655) ; FASEB J. 1997 Jun;11(7):509-16. (PMID: 9212074) Substance Nomenclature: 0 (Anion Transport Proteins) ; 0 (Carrier Proteins) ; 1806-98-0 (estradiol-17 beta-glucuronide) ; 26289-39-4 (S-(2,4-dinitrophenyl)glutathione) ; 4TI98Z838E (Estradiol) ; GAN16C9B8O (Glutathione) Entry Date(s): Date Created: 20000711 Date Completed: 20001205 Latest Revision: 20190818 Update Code: 20240513

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Biliary excretion of 17beta-estradiol 17beta-D-glucuronide is predominantly mediated by cMOAT/MRP2.