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Updated: Oct 3, 2025

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
Inhibiting uptake activity of organic anion transporter 2 by bile acids
Yu Wang1, Haihong Hu1, Jing Nie1
1Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Cancer Center of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310006, China.
Abstract:
Bile acids, a series of amphiphilic molecules, can interact with several drug transporters and impact drug ADME. Organic anion transporter 2 (OAT2) is exclusively expressed in the liver and kidney. However, the interaction between bile acids and hOAT2 is unelucidated. In this study, we observed that chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid, glycoursodeoxycholic acid (GUDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid, tauroursodeoxycholic acid could all inhibit uptake activity of hOAT2 while glycocholic acid (GCA) and cholic acid could not. Among them, TCDCA was the strongest inhibitor with IC50 value of 23.01 ± 3.45 μM and GCDCA was the second with IC50 value of 54.26 ± 5.47 μM. Meanwhile, GCA, GUDCA, TCA and TCDCA were identified as substrates of hOAT2. We further found that bile acid mixture (BA mix) could inhibit hOAT2-mediated uptake of cGMP, 5-fluorouracil, irinotecan and paclitaxel. BA mix could reduce the toxicity of paclitaxel to MDCK-hOAT2 cells. In addition, the uptake activity of three SNPs of hOAT2 (C329T, G571A, and G1514A) was all reduced. In conclusion, this study revealed bile acids could interact with hOAT2, providing new insight into the alteration of drug ADME and therapeutic effect mediated by hOAT2.
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