Mechanisms of hepatic transport of drugs: Implications for cholestatic drug reactions

Seminars in Liver Disease

Volumn 22, Issue 2, 2002, Pages 123-136

  Bohan, Alan ^a   Boyer, James L ^a  

^a Box 208019 ^*  (United States)

Author keywords

ABC transporters; Bile secretion; Cholestasis; Drug induced cholestasis; Genetic polymorphisms; Hepatocyte transport polypeptides; Nuclear receptors

Indexed keywords

4 AMINOHIPPURIC ACID; ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); BILE SALT; CARRIER PROTEIN; CHLOROQUINE; CHOLECYSTOKININ; CHOLINE; CIMETIDINE; CORTICOSTEROID; DACTINOMYCIN; DIGOXIN; DOPAMINE; ENALAPRIL; INDOMETACIN; METHOTREXATE; MEVINOLIN; MIDAZOLAM; NORADRENALIN; NUCLEOSIDE DERIVATIVE; OUABAIN; PRAVASTATIN; QUININE; QUININE DERIVATIVE; SALICYLIC ACID DERIVATIVE; SIMVASTATIN; TEMOCAPRILAT; UNINDEXED DRUG; VERAPAMIL; VINBLASTINE; XENOBIOTIC AGENT;

BILIARY EXCRETION; CHOLESTASIS; DISEASE PREDISPOSITION; DRUG INDUCED DISEASE; DRUG METABOLISM; DRUG TRANSPORT; DRUG UPTAKE; GENETIC POLYMORPHISM; HUMAN; LIVER METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ANIMALS; CARRIER PROTEINS; CHOLESTASIS; DISEASE MODELS, ANIMAL; HUMANS; LIVER; PHARMACEUTICAL PREPARATIONS; POLYMORPHISM, GENETIC; XENOBIOTICS;

EID: 0036256463     PISSN: 02728087     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2002-30099     Document Type: Review

References (147)

1. Manifestations of chemically induced liver damage
2. Drug-induced liver injury: Mechanisms and test systems
3. Molecular pathogenesis of cholestasis
4. Expression and regulation of hepatic drug and bile acid transporters
5. Molecular alterations in hepatocyte transport mechanisms in acquired cholestatic liver disorders
6. Molecular pathophysiology of membrane transport function in cholestasis
7. Molecular aspects of hepatobiliary transport
8. Drug-induced cholestasis: Pathogenesis and clinical features
9. Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2)
10. Inhibition of biliary glutathione secretion by cyclosporine A in the rat: Possible mechanisms and role in the cholestasis induced by the drug
11. Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis
12. Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats
13. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver
14. Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: In vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat
15. Cyclosporin A reduces canalicular membrane fluidity and regulates transporter function in rats
16. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions
17. Identification of a reactive metabolite of terbinafine: Insights into terbinafine-induced hepatotoxicity
18. Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes
19. Differential inhibition by cyclosporins of primary-active ATP-dependent transporters in the hepatocyte canalicular membrane
20. ATP-dependent export pumps and their inhibition by cyclosporins
21. Key challenges for toxicologists in the 21st century
22. Challenges and limitations of gene expression profiling in mechanistic and predictive toxicology
23. Toxicogenomics. Toxicologists brace for genomics revolution
24. Towards environmental toxicogenomics-development of a flow-through, high-density DNA hybridization array and its application to ecotoxicity assessment
25. Array of hope for gene technology
26. Application of genomics to the definition of the molecular basis for toxicity
27. Analysis of genetic and epigenetic mechanisms of toxicity: Potential roles of toxicogenomics and proteomics in toxicology
28. Microarrays and toxicology: The advent of toxicogenomics
29. Bile formation
30. Regulation of transmembrane electrical potential gradient in rat hepatocytes in situ
31. Cell membrane and transepithelial voltages and resistances in isolated rat hepatocyte couplets
32. Sinusoidal (basolateral) bile salt uptake systems of hepatocytes
33. +/bile acid cotransport system
34. +-bile acid cotransporter using peptide and fusion protein antibodies
35. Conjugate export pumps of the multidrug resistance protein (MRP) family: Localization, substrate specificity, and MRP2-mediated drug resistance
36. The role of mdr2 P-glycoprotein in hepatobiliary lipid transport
37. Expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver
38. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver
39. Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver
40. Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain
41. Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2
42. +-independent organic anion transporter
43. Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver
44. Assignment of the human organic anion transporting polypeptide (OATP) gene to chromosome 12p12 by fluorescence in situ hybridization
45. Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver
46. Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1
47. Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1
48. Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver
49. Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2
50. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (rapamycin)
51. Polymorphisms in OATP-C. Identification of multiple allelic variants associated with altered transport activity among European- and African-Americans
52. Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides
53. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta
54. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes
55. Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCTI and OCT2, mediating tubular secretion of cationic drugs
56. Functional characterization of an organic cation transporter (hOCTI) in a transiently transfected human cell line (HeLa)
57. Drug excretion mediated by a new prototype of polyspecific transporter
58. Cloning and characterization of two human polyspecific organic cation transporters
59. Xenobiotic-inducible transcription of cytochrome P450 genes
60. Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions
61. Phenobarbital response elements of cytochrome P450 genes and nuclear receptors
62. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity
63. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
64. Regulation of multidrug resistance-associated protein 2 (MRP2; ABCC2) by nuclear receptors PXR, FXR and CAR
65. Genetic analysis of the multidrug transporter
66. What have we learnt thus far from mice with disrupted P-glycoprotein genes?
67. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
68. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins
69. Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A
70. Molecular identification and functional characterization of mdr1a in rat cholangiocytes
71. Induction of Mdr1b expression by tumor necrosis factor-alpha in rat liver cells is independent of p53 but requires NF-kappaB signaling
72. Functional polymorphisms of the human multidrug-resistance gene: Multipie sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
73. Defect on multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis
74. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis
75. The wide spectrum of multidrug resistance 3 deficiency: From neonatal cholestasis to cirrhosis of adulthood
76. Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy
77. Mdr3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis
78. Identification of a sister gene to p-glycoprotein
79. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis
80. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein
81. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein
82. Structural, mechanistic and clinical aspects of MRP1
83. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologs of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines
84. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3)
85. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs
86. Canalicular transport of reduced glutathione in normal and mutant Eisai hyperbilirubinemic rats
87. MRP3, an organic anion transporter able to transport anti-cancer drugs
88. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver
89. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver
90. Charged amino acids in the transmembrane domains are involved in the determination of the substrate specificity of rat Mrp2
91. Single amino acid substitution of rat MRP2 results in acquired transport activity, for taurocholate
92. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2
93. Glutathione as a primary osmotic driving force in hepatic bile formation
94. The canalicular multispecific organic anion transporter mediates transport of reduced glutathione
95. Identification and characterization of high and low affinity transport systems for reduced glutathione in liver cell canalicular membranes
96. Hepatobiliary transport of glutathione and glutathione conjugate in rats with hereditary hyperbilirubinemia
97. Species differences in the transport activity for organic anions across the bile canalicular membrane
98. Cyclic AMP stimulates sorting of the canalicular multispecific organic anion transporter into the transcytotic bile secretory pathway in hepatocyte couplets
99. Protein kinase C-dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells
100. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver
101. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver
102. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome
103. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in Eisai hyperbilirubinemic rats
104. Characterization of inducible nature of MRP3 in rat liver
105. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells
106. +-dependent bile acid transporter in large but not small rat cholangiocytes
107. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter
108. Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver
109. Osmotic induction of signaling cascades: Role in regulation of cell function
110. Cell volume and bile acid excretion
111. Regulatory volume decrease stimulates bile flow, bile acid excretion, and exocytosis in isolated perfused rat liver
112. Effects of chronic choleretic infusions of bile acids on the membrane of the bile canaliculus
113. +/bile acid cotransporter in extrahepatic cholestasis
114. Regulation of sterol 27-hydroxylase and its role in the regulation of acidic pathway of bile acid biosynthesis in primary cultures of rat hepatocytes
115. Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver
116. +-taurocholate cotransport by translocating transporter to plasma membranes
117. +/taurocholate cotransport
118. Shortterm regulation of canalicular transport
119. Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver
120. 3- exchanger in rat hepatocytes
121. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets
122. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism
123. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha
124. Bile acids: Natural ligands for an orphan nuclear receptor
125. Identification of a nuclear receptor for bile acids
126. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR
127. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis
128. FXR, a bile acid receptor and biological sensor
129. Suppression of bile acid synthesis, but not of hepatic cholesterol 7alpha-hydroxylase expression, by obstructive cholestasis in humans
130. Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes
131. Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases
132. Cholestasis caused by inhibition of the adenosine triphosphate-dependent bile salt transport in rat liver
133. Enhancement of mdr2 gene transcription mediates the biliary transfer of phosphatidylcholine supplied by an increased biosynthesis in the pravastatin-treated rat
134. An autopsy case of troglitazone-induced fulminant hepatitis
135. Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone
136. Severe cholestasis related to itraconazole for the treatment of onychomycosis
137. Role of glutathione in the biliary excretion of the arsenical drugs trimelarsan and melarsoprol
138. Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes
139. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters
140. Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides oatp4 and oatp8 of rat and human liver
141. The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein
142. Transport of temocaprilat into rat hepatocytes: Role of organic anion transporting polypeptide
143. Localization and function of the organic anion-transporting polypeptide oatp2 in rat liver
144. Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells
145. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells
146. Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats
147. Induction of cMrp/cMoat gene expression by cisplatin, 2-acetylaminofluorene, or cycloheximide in rat hepatocytes