Human organic anion transporter 4 is a renal apical organic anion/decarboylate exchanger in the proximal tubules

• Ekaratanawong Sophapun

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine Department of Preclinical Sciences, Faculty of Medicine, Thammasat University

• Anzai Naohiko

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Jutabha Promsuk

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Miyazaki Hiroki

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Noshiro Rie

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Takeda Michio

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Kanai Yoshikatsu

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

• Sophasan Samaisukh

  Department of Physiology, Faculty of Science, Mahidol University

• Endou Hitoshi

  Department of Pharmacology and Toxicology, Kyorin University School of Medicine

書誌事項

タイトル別名

• Human Organic Anion Transporter 4 Is a Renal Apical Organic Anion/Dicarboxylate Exchanger in the Proximal Tubules

抄録

Human organic anion transporter OAT4 is expressed in the kidney and placenta and mediates high-affinity transport of estrone-3-sulfate (E₁S). Because a previous study demonstrated no trans-stimulatory effects by E₁S, the mode of organic anion transport via OAT4 remains still unclear. In the present study, we examined the driving force of OAT4 using mouse proximal tubular cells stably expressing OAT4 (S₂ OAT4). OAT4-mediated E₁S uptake was inhibited by glutarate (GA) (IC₅₀: 1.25 mM) and [¹⁴C]GA uptake via S₂ OAT4 was significantly trans-stimulated by unlabeled GA (5 mM) (P<0.001). [³H]E₁S uptake via S₂ OAT4 was significantly trans-stimulated by preloaded GA (P<0.001) and its [¹⁴C]GA efflux was significantly trans-stimulated by unlabeled E₁S in the medium (P<0.05). In additon, both the uptake and efflux of [¹⁴C]p-aminohippuric acid (PAH) and [¹⁴C]GA via S₂ OAT4 were significantly trans-stimulated by unlabeled GA or PAH. The immunoreactivities of OAT4 were observed in the apical membrane of proximal tubules along with those of basolateral organic anion/dicarboxylate exchangers such as hOAT1 and hOAT3 in the same tubular population. These results indicate that OAT4 is an apical organic anion/dicarboxylate exchanger and mainly functions as an apical pathway for the reabsorption of some organic anions in renal proximal tubules driven by an outwardly directed dicarboxylate gradient.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 94 (3), 297-304, 2004

  公益社団法人 日本薬理学会

キーワード

• organic anion
• dicarboxylate
• proximal tubule
• organic anion transporter

詳細情報

• CRID: 1390282680153835520
• NII論文ID: 130000073849
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.94.297
• COI: 1:CAS:528:DC%2BD2cXislCnu78%3D
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 6890263
• PubMed: 15037815
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6890263
• Web Site: https://search.jamas.or.jp/link/ui/2004230677
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可