Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells

Shinobu Mori, Hitomi Takanaga, Sumio Ohtsuki, Tsuneo Deguchi, Young Sook Kang, Ken ichi Hosoya, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

130 Citations (Scopus)

Abstract

The mechanism that removes homovanillic acid (HVA), an end metabolite of dopamine, from the brain is still poorly understood. The purpose of this study is to identify and characterize the brain-to-blood HVA efflux transporter at the rat blood-brain barrier (BBB). Using the Brain Efflux Index method, the apparent in vivo efflux rate constant of [3H]HVA from the brain, keff, was determined to be 1.69 × 10-2 minute-1. This elimination was significantly inhibited by paraaminohippuric acid (PAH), benzylpenicillin, indoxyl sulfate, and cimetidine, suggesting the involvement of rat organic anion transporter 3 (rOAT3). rOAT3-expressing oocytes exhibited [3H]HVA uptake (Km = 274 μmol/L), which was inhibited by several organic anions, such as PAH, indoxyl sulfate, octanoic acid, and metabolites of monoamine neurotransmitters. Neurotransmitters themselves did not affect the uptake. Furthermore, immunohistochemical analysis suggested that rOAT3 is localized at the abluminal membrane of brain capillary endothelial cells. These results provide the first evidence that rOAT3 is expressed at the abluminal membrane of the rat BBB and is involved in the brain-to-blood transport of HVA. This HVA efflux transport system is likely to play an important role in controlling the level of HVA in the CNS.

Original languageEnglish
Pages (from-to)432-440
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1

Keywords

  • Blood-brain barrier
  • Efflux transport
  • Homovanillic acid
  • Neurotransmitter metabolite
  • Organic anion transporter 3

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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