This study sought to clarify the contributions of organic anion-transporting polypeptide (OATP) 1B1 and 1B3 to the liver uptake of chenodeoxycholic acid (CDCA). We synthesized a fluorescent version of CDCA, chenodeoxychilyl-(Nepsilon-NBD)-lysine (CDCA-NBD), to characterize transporter-mediated uptake. CDCA-NBD is efficiently transported by OATP1B1 and OATP1B3 with high affinities. The Michaelis-Menten constants for CDCA-NBD uptake by OATP1B1 and OATP1B3 were 1.45 +/- 0.39 microM and 0.54 +/- 0.09 microM, respectively. By confocal laser scanning microscopy, CDCA-NBD, which is taken up by OATP1B1 and OATP1B3, was observed to localize to the cytosol. We also examined the transport of newly synthesized fluorescent bile acids. NBD-labeled bile acids, including cholic acid, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, were all transported by OATP1B1 and OATP1B3. CDCA-NBD exhibited the highest rate of transport of the five NBD-labeled bile acids examined in OATP1B1- and OATP1B3-expressing cells. Our results suggest that OATP1B1 and OATP1B3 play important roles in CDCA uptake into the liver. Fluorescent bile acids are useful tools to characterize the uptake properties of membrane transporters.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1194/jlr.M500532-JLR200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efflux and uptake transport and gut microbial reactivation of raloxifene glucuronides.
Basic Clin Pharmacol Toxicol
January 2025
Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Raloxifene has low bioavailability due to extensive glucuronidation in the intestine and the liver, and its pharmacokinetics is associated with high intra- and interindividual variability. Some of this variability could be explained by the enterohepatic recycling of raloxifene, which is driven by transporter-mediated uptake and efflux and gut microbial deglucuronidation of raloxifene glucuronides. These individual processes involved in raloxifene disposition, however, have not been characterized in full detail.
View Article and Find Full Text PDFEffect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.
Int J Mol Sci
December 2024
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan.
The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations.
View Article and Find Full Text PDFUltra-Sensitive Quantification of Coproporphyrin-I and -III in Human Plasma Using Ultra-Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.
ACS Omega
November 2024
Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Organic anion transporting polypeptides (OATP) 1B1 and 1B3 are expressed in liver cells and are involved in drug uptake in the liver. OATP1B activity varies due to polymorphisms and is decreased by OATP1B inhibitors. Variability of OATP1B activity impacts the pharmacokinetics of OATP1B substrate drugs through drug-drug interactions.
View Article and Find Full Text PDFBempedoic Acid, the First-in-Class Oral ATP Citrate Lyase Inhibitor with Hypocholesterolemic Activity: Clinical Pharmacology and Drug-Drug Interactions.
Pharmaceutics
October 2024
Centro di Ricerca Coordinata sulle Interazioni Farmacologiche, 20122 Milan, Italy.
Bempedoic acid is a new drug that improves the control of cholesterol levels, either as monotherapy or in combination with existing lipid-lowering therapies, and shows clinical efficacy in cardiovascular disease patients. Thus, patients with comorbidities and under multiple therapies may be eligible for bempedoic acid, thus facing the potential problem of drug-drug interactions (DDIs). Bempedoic acid is a prodrug administered orally at a fixed daily dose of 180 mg.
View Article and Find Full Text PDFAre Δ-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?
Int J Mol Sci
November 2024
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Article Synopsis
- Δ-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, and its usage among pregnant individuals is rising, leading to concerns about fetal exposure.
- Research indicates that fetal THC exposure is significantly lower than maternal levels due to a specific placental transporter that actively reduces THC transfer to the fetus, although the exact identity of this transporter remains unknown.
- In lab studies, it was discovered that THC and its metabolite THC-COOH acted as substrates for certain liver transporters but were not inhibitors, highlighting the complexity of THC metabolism and transport in the body.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!