Expression and functional involvement of organic anion transporting polypeptide subtype 3 (Slc21a7) in rat choroid plexus

Hiroyuki Kusuhara, Zhonggui He, Yoshinori Nagata, Yoshitane Nozaki, Takashi Ito, Hiroyuki Masuda, Peter J. Meier, Takaaki Abe, Yuichi Sugiyama

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Purpose. It has been shown that transport(s) are involved in the uptake of estradiol 17β glucuronide (E217βG) by the choroid plexus (CP). The purpose of this study is to compare the substrate specificity of the transporter in the CP with those of rat organic anion transporting polypeptide 1 (rOatp1) and rOatp3. Methods. The expression of rOatp1 and rOatp3 in rat CP was confirmed by RT-PCR and Western blot analyses. The substrate specificity of rOatp1 and rOatp3 was compared using cDNA-transfected LLC-PK1 cells. The uptake of E217βG by rat isolated CP was determined by centrifugal filtration technique. Results. PCR analyses demonstrated that the mRNA expression of rOatp3 was abundant in the CP, whereas that of rOatp1 was low. Immunohistochemical staining revealed that rOatp3 is expressed on the apical membrane of the CP. Kinetic parameters (Km and Ki values) of rOatp3 were similar to those for rOatp1. The results of mutual inhibition study suggest that E217βG and taurocholate share the same mechanism in the CP. Corticosterone, estrone-3-sulfate and indomethacin are moderate inhibitors, but no effects by digoxin, p-aminohippurate, benzylpenicillin and cimetidine were observed. Conclusions. rOatp3 is most possible candidate transporter involved in the uptake of organic anions on the brush border membrane of the choroid epithelial cells.

Original languageEnglish
Pages (from-to)720-727
Number of pages8
JournalPharmaceutical research
Volume20
Issue number5
DOIs
Publication statusPublished - 2003 May 1

Keywords

  • Blood-CSF barrier
  • Choroid plexus
  • Efflux transport
  • Oatp
  • Organic anion

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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