Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver

Hepatology ◽  
1997 ◽  
Vol 26 (6) ◽  
pp. 1667-1677 ◽  
Author(s):  
P J Meier ◽  
U Eckhardt ◽  
A Schroeder ◽  
B Hagenbuch ◽  
B Stieger
Keyword(s):  
Bile Acid ◽  
Substrate Specificity ◽  
Human Liver ◽  
Organic Anion ◽  
Anion Uptake

scholarly journals Effect of antisense oligonucleotides on the expression of hepatocellular bile acid and organic anion uptake systems in Xenopus laevis oocytes

1996 ◽  
Vol 316 (3) ◽  
pp. 901-904 ◽  
Author(s):  
Bruno HAGENBUCH ◽  
Bruce F. SCHARSCHMIDT ◽  
Peter J. MEIER
Keyword(s):  
Bile Acid ◽  
Xenopus Laevis ◽  
Rat Liver ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Organic Anion ◽  
Xenopus Laevis Oocytes ◽  
Acid Uptake ◽  
Uptake System ◽  
Anion Uptake

A Na+-dependent bile acid (Na+/taurocholate co-transporting polypeptide; Ntcp) and a Na+-independent bromosulphophthalein (BSP)/bile acid uptake system (organic-anion-transporting polypeptide; oatp) have been cloned from rat liver by using functional expression cloning in Xenopus laevis oocytes. To evaluate the extent to which these cloned transporters could account for overall hepatic bile acid and BSP uptake, we used antisense oligonucleotides to inhibit the expression of Ntcp and oatp in Xenopus laevis oocytes injected with total rat liver mRNA. An Ntcp-specific antisense oligonucleotide co-injected with total rat liver mRNA blocked the expression of Na+-dependent taurocholate uptake by approx. 95%. In contrast, an oatp-specific antisense oligonucleotide when co-injected with total rat liver mRNA had no effect on the expression of Na+-dependent taurocholate uptake, but it blocked Na+-independent uptake of taurocholate by approx. 80% and of BSP by 50%. Assuming similar expression of hepatocellular bile acid and organic anion transporters in Xenopus laevis oocytes, these results indicate that Ntcp and oatp respectively represent the major, if not the only, Na+-dependent and Na+-independent taurocholate uptake systems in rat liver. By contrast, the cloned oatp accounts for only half of BSP transport, suggesting that there must be additional, non-bile acid transporting organic anion uptake systems in rat liver.

scholarly journals Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver

Hepatology ◽  
2002 ◽  
Vol 36 (1) ◽  
pp. 164-172 ◽  
Author(s):  
Stephan R. Vavricka ◽  
Jessica Van Montfoort ◽  
Huy Riem Ha ◽  
Peter J. Meier ◽  
Karin Fattinger
Keyword(s):  
Human Liver ◽  
Organic Anion ◽  
Rifamycin Sv ◽  
Anion Uptake

scholarly journals Interindividual Diversity in Expression of Organic Anion Uptake Transporters in Normal and Cirrhotic Human Liver

2020 ◽  
Vol 4 (5) ◽  
pp. 739-752
Author(s):  
Tatsuya Taniguchi ◽  
Alana Zanetti‐Yabur ◽  
Pijun Wang ◽  
Mykhaylo Usyk ◽  
Robert D. Burk ◽  
...  
Keyword(s):  
Human Liver ◽  
Organic Anion ◽  
Uptake Transporters ◽  
Anion Uptake

Inhibition of rat hepatocyte organic anion transport by bile acids

1994 ◽  
Vol 267 (3) ◽  
pp. G458-G464
Author(s):  
K. Ishii ◽  
A. W. Wolkoff
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Organic Anion ◽  
High Capacity ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Organic Anions ◽  
Serum Bile Acid ◽  
High Affinity ◽  
Anion Uptake

Hepatocytes extract, metabolize, and excrete various bile acids and non-bile acid organic anions. The transporters for these two classes of compounds are unrelated, although the bromosulfophthalein (BSP)/bilirubin transporter can mediate Na(+)-independent transport of several bile acids. This may explain previous observations of inhibition of organic anion uptake by bile acids. It has been suggested that ursodeoxycholic acid (UDCA), which has been used to treat various hepatobiliary disorders, may not have this inhibitory effect. This possibility has now been studied. The influence of acute and chronic (overnight) exposure to UDCA and other bile acids on extraction of BSP from albumin by cultured rat hepatocytes has been examined. Two hepatocyte uptake systems have been identified, one of high affinity and low capacity and one of lower affinity and high capacity. The present study indicates that bile acids inhibit the high-affinity system but have little effect on the low-affinity system. These data suggest that extraction of organic anions from the circulation is modulated by bile acids. In states of cholestasis, where serum bile acid levels are abnormally high, organic anion uptake may be reduced as a consequence. This may serve to limit entry into the cell of potentially toxic compounds, such as bilirubin, for which detoxification and excretory mechanisms are compromised.

Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter

1998 ◽  
Vol 274 (1) ◽  
pp. G157-G169 ◽  
Author(s):  
Ann L. Craddock ◽  
Martha W. Love ◽  
Rebecca W. Daniel ◽  
Lyndon C. Kirby ◽  
Holly C. Walters ◽  
...  
Keyword(s):  
Bile Acid ◽  
Substrate Specificity ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Organic Anion ◽  
Hepatic Clearance ◽  
Tissue Expression ◽  
Independent Analysis ◽  
Rapid Amplification ◽  
Dependent Transport

The enterohepatic circulation of bile acids is maintained by Na+-dependent transport mechanisms. To better understand these processes, a full-length human ileal Na+-bile acid cotransporter cDNA was identified using rapid amplification of cDNA ends and genomic cloning techniques. Using Northern blot analysis to determine its tissue expression, we readily detected the ileal Na+-bile acid cotransporter mRNA in terminal ileum and kidney. Direct cloning and mapping of the transcriptional start sites confirmed that the kidney cDNA was identical to the ileal Na+-bile acid cotransporter. In transiently transfected COS cells, ileal Na+-bile acid cotransporter-mediated taurocholate uptake was strictly Na+dependent and chloride independent. Analysis of the substrate specificity in transfected COS or CHO cells showed that both conjugated and unconjugated bile acids are efficiently transported. When the inhibition constants for other potential substrates such as estrone-3-sulfate were determined, the ileal Na+-bile acid cotransporter exhibited a narrower substrate specificity than the related liver Na+-bile acid cotransporter. Whereas the multispecific liver Na+-bile acid cotransporter may participate in hepatic clearance of organic anion metabolites and xenobiotics, the ileal and renal Na+-bile acid cotransporter retains a narrow specificity for reclamation of bile acids.

scholarly journals Molecular cloning of two human liver 3 α-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder

1994 ◽  
Vol 299 (2) ◽  
pp. 545-552 ◽  
Author(s):  
Y Deyashiki ◽  
A Ogasawara ◽  
T Nakayama ◽  
M Nakanishi ◽  
Y Miyabe ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Human Liver ◽  
Polyclonal Antibodies ◽  
Amino Acid Sequences ◽  
Cdna Clones ◽  
Amino Acid Residues ◽  
Human Bile ◽  
Coding Regions ◽  
Computer Based

Human liver contains two dihydrodiol dehydrogenases, DD2 and DD4, associated with 3 alpha-hydroxysteroid dehydrogenase activity. We have raised polyclonal antibodies that cross-reacted with the two enzymes and isolated two 1.2 kb cDNA clones (C9 and C11) for the two enzymes from a human liver cDNA library using the antibodies. The clones of C9 and C11 contained coding sequences corresponding to 306 and 321 amino acid residues respectively, but lacked 5′-coding regions around the initiation codon. Sequence analyses of several peptides obtained by enzymic and chemical cleavages of the two purified enzymes verified that the C9 and C11 clones encoded DD2 and DD4 respectively, and further indicated that the sequence of DD2 had at least additional 16 residues upward from the N-terminal sequence deduced from the cDNA. There was 82% amino acid sequence identity between the two enzymes, indicating that the enzymes are genetic isoenzymes. A computer-based comparison of the cDNAs of the isoenzymes with the DNA sequence database revealed that the nucleotide and amino acid sequences of DD2 and DD4 are virtually identical with those of human bile-acid binder and human chlordecone reductase cDNAs respectively.

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