Organic anion-transporting polypeptide 1a4–mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules

Shin ichi Akanuma, Rintaro Kida, Ai Tsuchiyama, Masanori Tachikawa, Yoshiyuki Kubo, Ken ichi Hosoya

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.

Original languageEnglish
Pages (from-to)239-246
Number of pages8
JournalDrug metabolism and pharmacokinetics
Volume34
Issue number4
DOIs
Publication statusPublished - 2019 Aug

Keywords

  • Clearance
  • Hepatocyte
  • Heterogeneity
  • Liver
  • Oatp1a4
  • Organic anion-transporting polypeptide
  • Sulforhodamine-101
  • Zonation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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