Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver.

Abstract:

BACKGROUND & AIMS:Drug-induced cholestasis is a frequent form of acquired liver disease. To elucidate the molecular pathogenesis of drug-induced cholestasis, we investigated the effects of prototypic cholestatic drugs on the canalicular bile salt export pump (Bsep) of rat liver. METHODS:Vesicles were isolated from Bsep-, Mrp2-, and Bsep/Mrp2-expressing Sf9 cells. Canalicular plasma membrane (cLPM) vesicles from rat liver and Sf9 cell vesicles were used to study adenosine triphosphate (ATP)-dependent solute uptake by a rapid filtration technique. RESULTS:Bsep-expressing Sf9 cell vesicles showed ATP-dependent transport of numerous monoanionic bile salts with similar Michaelis constant values as in cLPM vesicles, whereas several known substrates of the multispecific organic anion transporter Mrp2 were not transported by Bsep. Cyclosporin A, rifamycin SV, rifampicin, and glibenclamide cis-inhibited Bsep-mediated bile salt transport to similar extents as ATP-dependent taurocholate transport in cLPM vesicles. In contrast, the cholestatic estrogen metabolite estradiol-17beta-glucuronide inhibited ATP-dependent taurocholate transport only in normal cLPM and in Bsep/Mrp2-coexpressing Sf9 cell vesicles, but not in Mrp2-deficient cLPM or in selectively Bsep-expressing Sf9 cell vesicles, indicating that it trans-inhibits Bsep only after its secretion into bile canaliculi by Mrp2. CONCLUSIONS:These results provide a molecular basis for previous in vivo observations and identify Bsep as an important target for induction of drug- and estrogen-induced cholestasis in mammalian liver.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Stieger B,Fattinger K,Madon J,Kullak-Ublick GA,Meier PJ

doi

10.1016/s0016-5085(00)70224-1

keywords:

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

422-30

issue

2

eissn

0016-5085

issn

1528-0012

pii

S0016508500987523

journal_volume

118

pub_type

杂志文章
  • Methemoglobinemia as a complication of 20% benzocaine spray for endoscopy.

    abstract::Topical 20% benzocaine (Hurricaine, Beutlich, Inc., Niles, Ill.) spray is frequently used for oral anesthesia before upper endoscopy. Side effects attributed to this agent are exceedingly rare. The author reports one of these rare complications, drug-induced methemoglobinemia, in a patient with methemoglobin reductase...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)91312-t

    authors: Collins JF

    更新日期:1990-01-01 00:00:00

  • Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene.

    abstract:BACKGROUND & AIMS:The Ki-RAS oncogene is altered in pancreatic ductal neoplasms. Pancreatic ductal cells (PDCs) were purified from cytokeratin 19 (K19)-Ki-RAS(G12V) transgenic mice and control littermates to identify properties of Ki-Ras activation in a cell-type-specific context. Because Ki-RAS mutation has prognostic...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2004.03.058

    authors: Schreiber FS,Deramaudt TB,Brunner TB,Boretti MI,Gooch KJ,Stoffers DA,Bernhard EJ,Rustgi AK

    更新日期:2004-07-01 00:00:00

  • The role of intraluminal junction potentials in the generation of the gastric potential difference in man.

    abstract::Using flowing isotonic NaCl or flowing molar KCl electrodes, the magnitude of liquid junction potentials between the electrode tip and gastric juice was measured directly, and calculated from electrolyte concentrations in gastric juice according to standard formulas. Gastric transepithelial potential difference was ob...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Read NW,Fordtran JS

    更新日期:1979-05-01 00:00:00

  • Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease.

    abstract::Increased dietary ratios of ω6/ω3 polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease (CD), but epidemiologic data are limited. We investigated whether variants of genes that control polyunsaturated fatty acid metabolism (CYP4F3, FADS1, and FADS2), along with the dietary ratio of ω6...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2013.12.034

    authors: Costea I,Mack DR,Lemaitre RN,Israel D,Marcil V,Ahmad A,Amre DK

    更新日期:2014-04-01 00:00:00

  • Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension.

    abstract:BACKGROUND & AIMS:Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase ...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1053/j.gastro.2019.11.296

    authors: Chalasani N,Abdelmalek MF,Garcia-Tsao G,Vuppalanchi R,Alkhouri N,Rinella M,Noureddin M,Pyko M,Shiffman M,Sanyal A,Allgood A,Shlevin H,Horton R,Zomer E,Irish W,Goodman Z,Harrison SA,Traber PG,Belapectin (GR-MD-02) Stud

    更新日期:2020-04-01 00:00:00

  • Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel syndrome?

    abstract:BACKGROUND & AIMS:Abdominal pain is the main symptom in patients with irritable bowel syndrome (IBS). Glycerol is an irritant of colonic mucosa. The aim of this study was to evaluate the effects of an intraluminal injection of glycerol on colonic motility and tone in patients with IBS and their modulation by drugs. ME...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/gast.1996.v110.pm8566580

    authors: Louvel D,Delvaux M,Staumont G,Camman F,Fioramonti J,Bueno L,Frexinos J

    更新日期:1996-02-01 00:00:00

  • Diphenylhydantoin-induced hepatic necrosis. A case study.

    abstract::A patient with post-traumatic seizure disorder developed lymphadenopathy, exfoliative dermatitis, and hepatic failure while on diphenylhydantoin therapy and died in hepatic coma. Autopsy disclosed massive hepatic necrosis. The clinical and pathological pictures are similar to the six previously reported cases of diphe...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:

    authors: Lee TJ,Carney CN,Lapis JL,Higgins T,Fallon HJ

    更新日期:1976-03-01 00:00:00

  • Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats.

    abstract:BACKGROUND & AIMS:Sex hormones have been reported to modulate visceral hypersensitivity (VH). Estrogen regulates neurons not only by binding to estrogen receptors (ERalpha and ERbeta) to initiate transcription but also via the G-protein coupled receptor GPR30, which binds and rapidly mediates actions of estrogen. We ex...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.03.047

    authors: Lu CL,Hsieh JC,Dun NJ,Oprea TI,Wang PS,Luo JC,Lin HC,Chang FY,Lee SD

    更新日期:2009-09-01 00:00:00

  • Functional expression of the canalicular bile salt export pump of human liver.

    abstract:BACKGROUND & AIMS:Hepatic bile salt secretion is an essential function of vertebrate liver. Rat and mouse bile salt export pump (Bsep) are adenosine triphosphate (ATP)-dependent bile salt transporters. Mutations in human BSEP were identified as the cause of progressive familial intrahepatic cholestasis type 2. BSEP pro...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2002.36587

    authors: Noé J,Stieger B,Meier PJ

    更新日期:2002-11-01 00:00:00

  • Ventromedial hypothalamic lesions increase gastrointestinal DNA synthesis through vagus nerve in rats.

    abstract:BACKGROUND:It was recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in gastrointestinal DNA content in rats. In the present study, the mechanism of this alteration was examined. METHODS:The DNA content and synthesis after VMH lesioning in rat gastrointestinal tracts were determined. ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(93)90416-a

    authors: Kiba T,Tanaka K,Endo O,Inoue S

    更新日期:1993-02-01 00:00:00

  • E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex.

    abstract:BACKGROUND & AIMS:Early metastasis is a hallmark of pancreatic ductal adenocarcinoma and responsible for >90% of pancreatic cancer death. Because little is known about the biology and genetics of the metastatic process, we desired to elucidate molecular pathways mediating pancreatic cancer metastasis in vivo by an unbi...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.04.004

    authors: von Burstin J,Eser S,Paul MC,Seidler B,Brandl M,Messer M,von Werder A,Schmidt A,Mages J,Pagel P,Schnieke A,Schmid RM,Schneider G,Saur D

    更新日期:2009-07-01 00:00:00

  • Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice.

    abstract:BACKGROUND & AIMS:The mechanism by which antimicrobial therapy against Helicobacter pylori is enhanced by acid suppression is unknown. The aim of this study was to investigate the effect of omeprazole on gastric juice, plasma, and saliva concentrations of metronidazole, amoxicillin, and clarithromycin. METHODS:Single ...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/gast.1996.v111.pm8690200

    authors: Goddard AF,Jessa MJ,Barrett DA,Shaw PN,Idström JP,Cederberg C,Spiller RC

    更新日期:1996-08-01 00:00:00

  • Ablation of Foxl1-Cre-labeled hepatic progenitor cells and their descendants impairs recovery of mice from liver injury.

    abstract:BACKGROUND & AIMS:Foxl1(+) hepatic progenitor cells (HPCs) differentiate into cholangiocytes and hepatocytes after liver injury. We investigated the requirement for Foxl1(+) HPCs in recovery from liver injury in mice. METHODS:We developed mice in which we could trace and delete Foxl1-expressing HPCs and their descenda...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2014.09.039

    authors: Shin S,Upadhyay N,Greenbaum LE,Kaestner KH

    更新日期:2015-01-01 00:00:00

  • Effects of cisapride on jejunal motor activity in fasting healthy humans.

    abstract::The effects of cisapride on jejunal interdigestive motor activity were studied in 12 healthy men participating in three experiments each. Five minutes after an activity front (phase III) they received, in random double-blind fashion, 10 mg of cisapride, 4 mg of cisapride, or saline placebo by intravenous injection. Mo...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/0016-5085(86)90387-2

    authors: Stacher G,Steinringer H,Schneider C,Winklehner S,Mittelbach G,Gaupmann G

    更新日期:1986-05-01 00:00:00

  • Thermal stress-induced HSP70 mediates protection against intrapancreatic trypsinogen activation and acute pancreatitis in rats.

    abstract:BACKGROUND & AIMS:Prior thermal stress induces heat shock protein 70 (HSP70) expression in the pancreas and protects against secretagogue-induced pancreatitis, but it is not clear that this thermal stress-induced protection is actually mediated by HSP70 since thermal stress may have other, non-HSP related, effects. ME...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2002.30314

    authors: Bhagat L,Singh VP,Song AM,van Acker GJ,Agrawal S,Steer ML,Saluja AK

    更新日期:2002-01-01 00:00:00

  • Quantitative fecal indium 111-labeled leukocyte excretion in the assessment of disease in Crohn's disease.

    abstract::The assessment of disease activity in Crohn's disease involves determination of either clinical indexes (e.g., Crohn's disease activity index) or laboratory measurements (e.g., C-reactive protein and erythrocyte sedimentation rate). These have the disadvantage of being indirect and nonspecific correlates of gut inflam...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Saverymuttu SH,Peters AM,Lavender JP,Pepys MB,Hodgson HJ,Chadwick VS

    更新日期:1983-12-01 00:00:00

  • Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat.

    abstract:BACKGROUND & AIMS:Thromboxane levels correlate with severity of liver injury in rats given alcohol. The aim of this study was to evaluate the effect of thromboxane inhibitors on pathological changes in experimental alcoholic liver disease. METHODS:Male Wistar rats were given a liquid diet and ethanol intragastrically ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(97)70236-1

    authors: Nanji AA,Khwaja S,Rahemtulla A,Miao L,Zhao S,Tahan SR

    更新日期:1997-01-01 00:00:00

  • Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis.

    abstract:BACKGROUND & AIMS:The anti-cancer effects of vegetables and fruit have been investigated extensively, but the association between vegetable and fruit consumption and risk of hepatocellular carcinoma (HCC) has not been quantified. We performed a meta-analysis of observational studies to clarify the association. METHODS...

    journal_title:Gastroenterology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1053/j.gastro.2014.08.005

    authors: Yang Y,Zhang D,Feng N,Chen G,Liu J,Chen G,Zhu Y

    更新日期:2014-11-01 00:00:00

  • Effects of streptozotocin-diabetes on rat intestinal mucin and goblet cells.

    abstract::Intestinal mucin and goblet cells were examined in streptozotocin-diabetic rats and age-matched controls. Mucin (tissue content and secretion) was measured using a highly specific enzyme-linked immunoassay. In contrast to the increased protein to deoxyribonucleic acid ratio, an absolute decrease was observed in the mu...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(89)91417-0

    authors: Mantle M,Thakore E,Atkins E,Mathison R,Davison JS

    更新日期:1989-07-01 00:00:00

  • Inflammation-Induced Expression and Secretion of MicroRNA 122 Leads to Reduced Blood Levels of Kidney-Derived Erythropoietin and Anemia.

    abstract:BACKGROUND & AIMS:Anemia is associated commonly with acute and chronic inflammation, but the mechanisms of their interaction are not clear. We investigated whether microRNA 122 (MIR122), which is generated in the liver and is secreted into the blood, is involved in the development of anemia associated with inflammation...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2016.07.031

    authors: Rivkin M,Simerzin A,Zorde-Khvalevsky E,Chai C,Yuval JB,Rosenberg N,Harari-Steinfeld R,Schneider R,Amir G,Condiotti R,Heikenwalder M,Weber A,Schramm C,Wege H,Kluwe J,Galun E,Giladi H

    更新日期:2016-11-01 00:00:00

  • Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms.

    abstract:BACKGROUND & AIMS:Germline mutations in one of four mismatch repair genes have been found in the majority of families with hereditary nonpolyposis colorectal cancer (HNPCC), but only in a small part of families with atypical HNPCC. The recently cloned EXO1 gene might be involved in the pathogenesis of HNPCC because the...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2001.25117

    authors: Wu Y,Berends MJ,Post JG,Mensink RG,Verlind E,Van Der Sluis T,Kempinga C,Sijmons RH,van der Zee AG,Hollema H,Kleibeuker JH,Buys CH,Hofstra RM

    更新日期:2001-06-01 00:00:00

  • Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers.

    abstract::The transport of folic acid was investigated in organ-cultured endoscopic biopsy specimens of intestinal mucosa from normal subjects. In the proximal small intestine at pH 5.5 and 6.5, [3H]folic acid accumulated to concentrations 2.64- and 2.17-fold higher than those of the medium, respectively, but at pH 7.5 the conc...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(90)90614-7

    authors: Zimmerman J

    更新日期:1990-10-01 00:00:00

  • Genetics of Familial and Sporadic Pancreatic Cancer.

    abstract::In the previous decade, comprehensive genomic analyses have yielded important insights about the genetic alterations that underlie pancreatic tumorigenesis. Whole-exome and whole-genome sequencing of pancreatic ductal adenocarcinomas have confirmed the critical driver genes altered in the majority of pancreatic cancer...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2018.12.039

    authors: Wood LD,Yurgelun MB,Goggins MG

    更新日期:2019-05-01 00:00:00

  • Colonic and small intestinal alkaline phosphatase. A histochemical and biochemical study.

    abstract::Colonic and intestinal alkaline phosphatase were studied histoenzymatically and biochemically in normal mucosae from eight hemicolectomy specimens. Histochemically, the most intense reaction was found in the small intestine, followed by vascular endothelium and colonic epithelium, respectively. The reaction was strong...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Lev R,Griffiths WC

    更新日期:1982-06-01 00:00:00

  • Disordered gustatory acuity in liver disease.

    abstract::Disordered gustatory acuity was demonstrated in 22 patients with acute viral hepatitis and in 16 patients with chronic liver disease utilizing subjective responses and objective measurements of detection and recognition thresholds and scaling for NaCl, sucrose, HCl, and urea. In patients with early hepatitis and those...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Smith FR,Henkin RI,Dell RB

    更新日期:1976-04-01 00:00:00

  • Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C.

    abstract:BACKGROUND & AIMS:The host immune response during the chronic phase of hepatitis C virus infection varies among individuals; some patients have a no interferon (IFN) response in the liver, whereas others have full activation of IFN-stimulated genes (ISGs). Preactivation of this endogenous IFN system is associated with ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2010.11.039

    authors: Dill MT,Duong FH,Vogt JE,Bibert S,Bochud PY,Terracciano L,Papassotiropoulos A,Roth V,Heim MH

    更新日期:2011-03-01 00:00:00

  • Fiberoptic endoscopy during laparotomy in the diagnosis of small intestinal bleeding.

    abstract::A patient with recurrent gastrointestinal bleeding caused by hereditary hemorrhagic telangiectasia localized to the small intestine is described. The diagnosis was made by combining two recognized investigational tools-fiberoptic endoscopy and laparotomy. ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Greenberg GR,Phillips MJ,Tovee EB,Jeejeebhoy KN

    更新日期:1976-07-01 00:00:00

  • Structural features of absorptive cell and microvillus membrane preparations from rat small intestine.

    abstract::Absorptive cells of the small intestine are highly polarized cells with distinct microvillus membrane (MVM) and basolateral plasma membrane domains. We compared membrane structure in the following preparations of rat small intestine commonly used for in vitro study of MVM function: epithelial sheets, isolated epitheli...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(86)90194-0

    authors: Bjorkman DJ,Allan CH,Hagen SJ,Trier JS

    更新日期:1986-12-01 00:00:00

  • Colonic epithelial functional phenotype varies with type and phase of experimental colitis.

    abstract:BACKGROUND & AIMS:Colonic crypt elongation occurs during both chronic colitis and in the recovery phase of acute colitis. The impact of these alterations on epithelial cell functions is not fully defined. METHODS:DNA microarray analysis of freshly isolated colonic epithelial cells (CECs) from acute and chronic colitis...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/s0016-5085(03)00665-6

    authors: Mizoguchi E,Xavier RJ,Reinecker HC,Uchino H,Bhan AK,Podolsky DK,Mizoguchi A

    更新日期:2003-07-01 00:00:00

  • Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells.

    abstract:BACKGROUND & AIMS:The Raf kinase inhibitor protein (RKIP) has been identified as a suppressor of the mitogen-activated protein kinase (MAPK) pathway. Loss of RKIP function promotes tumor metastasis in prostate cancer and melanoma. The insulin-like growth factor I (IGF-I)-mediated MAPK cascade is often activated in hepa...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2006.07.012

    authors: Lee HC,Tian B,Sedivy JM,Wands JR,Kim M

    更新日期:2006-10-01 00:00:00