scholarly journals Organic anion-transporting polypeptide 1b2 (Oatp1b2) is important for the hepatic uptake of unconjugated bile acids: Studies in Oatp1b2-null mice

Hepatology ◽  
2010 ◽  
Vol 53 (1) ◽  
pp. 272-281 ◽  
Author(s):  
Iván L. Csanaky ◽  
Hong Lu ◽  
Youcai Zhang ◽  
Kenichiro Ogura ◽  
Supratim Choudhuri ◽  
...  
Keyword(s):  
Bile Acids ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporting Polypeptide

scholarly journals Characterization of Organic Anion Transporting Polypeptide 1b2-null Mice: Essential Role in Hepatic Uptake/Toxicity of Phalloidin and Microcystin-LR

2008 ◽  
Vol 103 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Hong Lu ◽  
Supratim Choudhuri ◽  
Kenichiro Ogura ◽  
Iván L. Csanaky ◽  
Xiaohong Lei ◽  
...  
Keyword(s):  
Essential Role ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporting Polypeptide

Fentanyl Pharmacokinetics is not Dependent on Hepatic Uptake by Organic Anion-Transporting Polypeptide 1B1 in Human Beings

2013 ◽  
Vol 113 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Victoria C. Ziesenitz ◽  
Sonja K. König ◽  
Nina Mahlke ◽  
Ricarda Jantos ◽  
Gisela Skopp ◽  
...  
Keyword(s):  
Organic Anion ◽  
Hepatic Uptake ◽  
Human Beings ◽  
Organic Anion Transporting Polypeptide

Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake

2003 ◽  
Vol 285 (5) ◽  
pp. G829-G839 ◽  
Author(s):  
Soichiro Hata ◽  
Pijun Wang ◽  
Nicole Eftychiou ◽  
Meenakshisundaram Ananthanarayanan ◽  
Ashok Batta ◽  
...  
Keyword(s):  
Bile Acids ◽  
Competitive Inhibition ◽  
Organic Anion ◽  
Inducible Promoter ◽  
Hydroxyl Groups ◽  
Organic Anion Transporting Polypeptide ◽  
Hela Cell Lines ◽  
Dependent Transport

Transport of a series of3H-radiolabeled C23, C24, and C27bile acid derivatives was compared and contrasted in HeLa cell lines stably transfected with rat Na+/taurocholate cotransporting polypeptide (ntcp) or organic anion transporting polypeptide 1 (oatp1) in which expression was under regulation of a zinc-inducible promoter. Similar uptake patterns were observed for both ntcp and oatp1, except that unconjugated hyodeoxycholate was a substrate of oatp1 but not ntcp. Conjugated bile acids were transported better than nonconjugated bile acids, and the configuration of the hydroxyl groups (α or β) had little influence on uptake. Although cholic and 23 norcholic acids were transported by ntcp and oatp1, other unconjugated bile acids (chenodeoxycholic, ursodeoxycholic) were not. In contrast to ntcp, oatp1-mediated uptake of the trihydroxy bile acids taurocholate and glycocholate was four- to eightfold below that of the corresponding dihydroxy conjugates. Ntcp mediated high affinity, sodium-dependent transport of [35S]sulfobromophthalein with a Kmsimilar to that of oatp1-mediated transport of [35S]sulfobromophthalein ( Km= 3.7 vs. 3.3 μM, respectively). In addition, for both transporters, uptake of sulfobromophthalein and taurocholic acid showed mutual competitive inhibition. These results indicate that the substrate specificity of ntcp is considerably broader than previously suspected and caution the extrapolation of transport data obtained in vitro to physiological function in vivo.

scholarly journals OATP1B3-1B7, a novel organic anion transporting polypeptide, is modulated by FXR ligands and transports bile acids

2019 ◽  
Vol 317 (6) ◽  
pp. G751-G762 ◽  
Author(s):  
Vanessa Malagnino ◽  
Janine Hussner ◽  
Ali Issa ◽  
Angela Midzic ◽  
Henriette E. Meyer zu Schwabedissen
Keyword(s):  
Endoplasmic Reticulum ◽  
Bile Acid ◽  
Bile Acids ◽  
Smooth Endoplasmic Reticulum ◽  
Organic Anion ◽  
Farnesoid X Receptor ◽  
Organic Anion Transporter ◽  
Organic Anion Transporting Polypeptide ◽  
Anion Transporter ◽  
Solute Carrier

Organic anion transporting polypeptide (OATP) 1B3–1B7 (LST-3TM12) is a member of the OATP1B [solute carrier organic anion transporter ( SLCO) 1B] family. This transporter is not only functional but also expressed in the membrane of the smooth endoplasmic reticulum of hepatocytes and enterocytes. OATP1B3–1B7 is a splice variant of SLCO1B3 in which the initial part is encoded by SLCO1B3, whereas the rest of the mRNA originates from the gene locus of SLCO1B7. In this study, we not only showed that SLCO1B3 and the mRNA encoding for OATP1B3–1B7 share the 5′ untranslated region but also that silencing of an initial SLCO1B3 exon lowered the amount of SLCO1B3 and of SLCO1B7 mRNA in Huh-7 cells. To validate the assumption that both transcripts are regulated by the same promoter we tested the influence of the bile acid sensor farnesoid X receptor (FXR) on their transcription. Treatment of Huh-7 and HepaRG cells with activators of this known regulator of OATP1B3 not only increased SLCO1B3 but also OATP1B3–1B7 mRNA transcription. Applying a heterologous expression system, we showed that several bile acids interact with OATP1B3–1B7 and that taurocholic acid and lithocholic acid are OATP1B3–1B7 substrates. As OATP1B3–1B7 is located in the smooth endoplasmic reticulum, it may grant access to metabolizing enzymes. In accordance are our findings showing that the OATP1B3–1B7 inhibitor bromsulphthalein significantly reduced uptake of bile acids into human liver microsomes. Taken together, we report that OATP1B3–1B7 transcription can be modulated with FXR agonists and antagonists and that OATP1B3–1B7 transports bile acids. NEW & NOTEWORTHY Our study on the transcriptional regulation of the novel organic anion transporting polypeptide (OATP) 1B3–1B7 concludes that the promoter of solute carrier organic anion transporter ( SLCO) 1B3 governs SLCO1B3–1B7 transcription. Moreover, the transcription of OATP1B3–1B7 can be modulated by farnesoid X receptor (FXR) agonists and antagonists. FXR is a major regulator in bile acid homeostasis that links OATP1B3–1B7 to this physiological function. Findings in transport studies with OATP1B3–1B7 suggest that this transporter interacts with the herein tested bile acids.

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