Measurement of bile salt export pump transport activities using a fluorescent bile acid derivative

Kana Yamaguchi, Tsuyoshi Murai, Hikaru Yabuuchi, Shu Ping Hui, Takao Kurosawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

A novel fluorescent bile acid derivative, 4-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole-conjugated bile acid was synthesized as a probe to develop a rapid screening method for function analysis of bile salt export pump (BSEP, ABCB 11). The transport properties of the synthetic fluorescent bile acid derivative in membrane vesicles obtained from hBSEP-expressing Sf9 cells were examined using the liquid chromatography-electrospray ionization-mass spectrometry method. The Michaelis-Menten constant and maximum uptake rate for the synthetic fluorescent bile acid derivative by hBSEP were 23.1±1.6 μM and 623.2± 22.4 pmol/min/mg protein, respectively. These kinetic parameters of the synthetic fluorescent bile acid derivative were comparable with those of an unlabeled bile acid, taurocholic acid. Moreover, we examined inhibitory effects of various drugs on hBSEP-mediated uptake of the fluorescent bile acid derivative using a fluorescence detection method. The relative uptake activities (percent of control) for the fluorescent bile acid derivative in the presence of an inhibitor were in accordance with previous findings using 3H-labeled taurocholic acid. Our results suggest that the synthetic fluorescent bile acid derivative may be useful for evaluation of the inhibitory effects of various drugs on hBSEP-mediated uptake.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalDrug Metabolism and Pharmacokinetics
Volume25
Issue number2
DOIs
Publication statusPublished - 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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