Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins

Hikaru Yabuuchi, Kenji Tanaka, Miyako Maeda, Masaaki Takemura, Masaki Oka, Rikiya Ohashi, Ikumi Tamai

研究成果: Article査読

29 被引用数 (Scopus)

抄録

The dog bile salt export pump (BSEP; ABCB11) was cloned and expressed in a Sf9 insect cell system. The deduced amino acid sequence encodes a 1325-amino-acid protein, which shows 89.4% and 80.2% homology with human BSEP and rat Bsep, respectively. The transcript of the dog Bsep gene was detected at a high level in liver, but not other tissues, by quantitative RT-PCR. The BSEP-expressing membrane vesicles isolated from Sf9 cells exhibited saturable uptake of [3H]taurocholic acid with Michaelis constants (Km) of 33.7, 22.2 and 19.9 μM for the dog, rat and human transporters, respectively. The uptake of [3H]taurocholic acid by all three transporters was significantly inhibited by troglitazone, glibenclamide, and other several inhibitors, while pravastatin inhibited dog Bsep and human BSEP, but not rat Bsep at 100 μM. The IC50 of troglitazone for dog Bsep, human BSEP, and rat Bsep were 32, 20, and 60 μM, and those of pravastatin were 441, 240 and > 1,000 μM, respectively. In conclusion, while dog Bsep shows similar ATP-dependent bile acid transport characteristics to human BSEP and rat Bsep, there is a species difference in affinity for drugs such as pravastatin and troglitazone.

本文言語English
ページ(範囲)441-448
ページ数8
ジャーナルBiopharmaceutics and Drug Disposition
29
8
DOI
出版ステータスPublished - 2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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