Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs

Yuki Kanado, Yuya Tsurudome, Yuji Omata, Sai Yasukochi, Naoki Kusunose, Takahiro Akamine, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

研究成果: ジャーナルへの寄稿記事

抄録

P-glycoprotein (P-gp/ABCB1) is an ATP-binding cassette drug efflux transporter expressed in a variety of tissues that affects the pharmacokinetic disposition of many drugs. Although several studies have reported gender-dependent differences in the expression of P-gp, the role of sex hormones in regulating the expression of P-gp and its transport activity has not been well understood. In this study, we demonstrated that 17β-estradiol has the ability to induce the expression of P-pg in mouse kidneys and cultured human renal proximal tubular epithelial cells. After intravenous injection of a typical P-gp substrate, digoxin, renal clearance in female mice was approximately 2-fold higher than that in male mice. The expression of murine P-gp and its mRNA (Abcb1a and Abcb1b) were also higher in female mice than in male mice. The expression of P-gp in cultured renal tissues prepared from female and male mice was significantly increased by 17β-estradiol, but not testosterone. Similar 17β-estradiol-induced expression of P-gp was also detected in cultured human tubular epithelial cells, accompanied by the enhancement of its transport activity of digoxin. The present findings suggest the contribution of estradiol to female-predominant expression of P-gp in renal cells, which is associated with sex-related disparities in the renal elimination of digoxin.

元の言語英語
ページ(範囲)613-619
ページ数7
ジャーナルBiochemical and Biophysical Research Communications
519
発行部数3
DOI
出版物ステータス出版済み - 11 12 2019

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P-Glycoprotein
Estradiol
Digoxin
Epithelial Cells
Kidney
Pharmaceutical Preparations
Tissue
Pharmacokinetics
Gonadal Steroid Hormones
Testosterone
Adenosine Triphosphate
Intravenous Injections
Messenger RNA
Substrates

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. / Kanado, Yuki; Tsurudome, Yuya; Omata, Yuji; Yasukochi, Sai; Kusunose, Naoki; Akamine, Takahiro; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro.

:: Biochemical and Biophysical Research Communications, 巻 519, 番号 3, 12.11.2019, p. 613-619.

研究成果: ジャーナルへの寄稿記事

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AU - Yasukochi, Sai

AU - Kusunose, Naoki

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