PDZK1 Regulates Organic Anion Transporting Polypeptide Oatp1a in Mouse Small Intestine

• SUGIURA Tomoko

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• OTAKE Toru

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• SHIMIZU Takuya

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• WAKAYAMA Tomohiko

  Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University

• SILVER David L.

  Department of Biochemistry, Albert Einstein College of Medicine

• UTSUMI Rie

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• NISHIMURA Tomohiro

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• ISEKI Shoichi

  Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University

• NAKAMICHI Noritaka

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• KUBO Yoshiyuki

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• TSUJI Akira

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

• KATO Yukio

  Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Science, Kanazawa University

Bibliographic Information

Other Title

• PDZK1 Regulates Organic Anion Transporting Polypeptide Oatpla in Mouse Small Intestine

Abstract

  Recent studies indicate that various members of the organic anion transporting polypeptide (OATP) family are expressed on apical membranes of the small intestine. In the present study, we investigated possible interaction of Oatp with the PDZ protein PDZK1 in mouse small intestine, using [³H]estrone-3-sulfate (E3S) as a typical substrate. After intraduodenal administration, the level of [³H]E3S appearing in the portal vein of pdzk1 gene knockout (pdzk1^−/−) mice was much lower than that in wild-type mice. Lower intestinal absorption of [³H]E3S in pdzk1^−/− mice was confirmed in Ussing-type chamber experiments, which showed smaller uptake of [³H]E3S from the apical side in intestinal tissues of pdzk1^−/− mice compared with wild-type mice. The kinetics and inhibition profile of [³H]E3S uptake in the Ussing-type chamber were similar to those in HEK293 cells stably expressing Oatp1a5, suggesting involvement of Oatp1a5 in [³H]E3S uptake. Immunoreactivity to anti-Oatp1a antibody was colocalized with PDZK1 in the small intestine of wild-type mice, whereas apical localization of Oatp1a protein was reduced in pdzk1^−/− mice. An immunoprecipitation study revealed physical interaction of PDZK1 with Oatp1a. Thus, PDZK1 appears to act as an adaptor for Oatp1a. This is the first demonstration of a regulatory protein directly interacting with small-intestinal OATP.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 25 (6), 588-598, 2010

  The Japanese Society for the Study of Xenobiotics

Keywords

• PDZ protein
• protein-protein interactions
• PDZK1
• OATP
• SLC transporters
• intestinal absorption
• extrone-3-sulfate

Details

• CRID: 1390282680155477504
• NII Article ID: 10027743926
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.dmpk-10-rg-074
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300720?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300720?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2011287561
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed