PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine

Tomoko Sugiura, Toru Otake, Takuya Shimizu, Tomohiko Wakayama, David L. Silver, Rie Utsumi, Tomohiro Nishimura, Shoichi Iseki, Noritaka Nakamichi, Yoshiyuki Kubo, Akira Tsuji, Yukio Kato

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)588-598
Number of pages11
JournalDrug Metabolism and Pharmacokinetics
Volume25
Issue number6
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Small Intestine
Anions
Peptides
Gene Knockout Techniques
HEK293 Cells
Intestinal Absorption
Portal Vein
Immunoprecipitation
Knockout Mice
estrone sulfate
Anti-Idiotypic Antibodies
Proteins
Membranes

Keywords

  • Extrone-3-sulfate
  • Intestinal absorption
  • OATP
  • PDZ protein
  • PDZK1
  • Protein-protein interactions
  • SLC transporters

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science

Cite this

Sugiura, T., Otake, T., Shimizu, T., Wakayama, T., Silver, D. L., Utsumi, R., ... Kato, Y. (2010). PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine. Drug Metabolism and Pharmacokinetics, 25(6), 588-598.

PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine. / Sugiura, Tomoko; Otake, Toru; Shimizu, Takuya; Wakayama, Tomohiko; Silver, David L.; Utsumi, Rie; Nishimura, Tomohiro; Iseki, Shoichi; Nakamichi, Noritaka; Kubo, Yoshiyuki; Tsuji, Akira; Kato, Yukio.

In: Drug Metabolism and Pharmacokinetics, Vol. 25, No. 6, 2010, p. 588-598.

Research output: Contribution to journalArticle

Sugiura, T, Otake, T, Shimizu, T, Wakayama, T, Silver, DL, Utsumi, R, Nishimura, T, Iseki, S, Nakamichi, N, Kubo, Y, Tsuji, A & Kato, Y 2010, 'PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine', Drug Metabolism and Pharmacokinetics, vol. 25, no. 6, pp. 588-598.
Sugiura T, Otake T, Shimizu T, Wakayama T, Silver DL, Utsumi R et al. PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine. Drug Metabolism and Pharmacokinetics. 2010;25(6):588-598.
Sugiura, Tomoko ; Otake, Toru ; Shimizu, Takuya ; Wakayama, Tomohiko ; Silver, David L. ; Utsumi, Rie ; Nishimura, Tomohiro ; Iseki, Shoichi ; Nakamichi, Noritaka ; Kubo, Yoshiyuki ; Tsuji, Akira ; Kato, Yukio. / PDZK1 regulates organic anion transporting polypeptide oatp1a in mouse small intestine. In: Drug Metabolism and Pharmacokinetics. 2010 ; Vol. 25, No. 6. pp. 588-598.
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