pH-dependent transport kinetics of the human organic anion-transporting polypeptide 1A2

Tokio Morita, Takeshi Akiyoshi, Ryo Sato, Kazuhiro Katayama, Kodai Yajima, Hiroki Kataoka, Ayuko Imaoka, Yoshikazu Sugimoto, Hisakazu Ohtani

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Organic anion-transporting polypeptide (OATP) 1A2 is expressed on the apical sides of intestinal and renal epithelial cells and considered to be involved in the intestinal absorption and renal reabsorption of drugs. Although the transport activity of OATP1A2 is considered to be pH-dependent, the effects of pH on its kinetic parameters and on the potency of OATP1A2 inhibitors are yet to be elucidated. Some OATP are known to have multiple binding sites (MBS), but it remains unclear whether OATP1A2 has MBS. In the present study, we evaluated the influence of pH on the OATP1A2-mediated uptake of estrone 3-sulfate using OATP1A2-expressing HEK293 cells. The uptake of 0.3 μM estrone 3-sulfate by HEK293-OATP1A2 cells was pH-dependent. OATP1A2 exhibited bimodal saturation kinetics at pH 6.3 and 7.4. Compared with that seen at pH 6.3 (5.62 μM), the Km value of the high-affinity site was 8-fold higher at pH 7.4 (43.2 μM). In addition, the influence of pH on the potency of inhibitors varied among the examined inhibitors. These results suggest that the transport properties of OATP1A2 under lower pH conditions, such as those found in the microenvironments of the small intestinal mucosa and distal tubules, differ from those seen under neutral pH conditions.

Original languageEnglish
Pages (from-to)220-227
Number of pages8
JournalDrug Metabolism And Pharmacokinetics
Issue number2
Publication statusPublished - 2020 Apr


  • Multiple binding site
  • OATP1A2
  • Uptake transporter
  • pH-dependency

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)


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