β-Alanine and l-histidine transport across the inner blood-retinal barrier: Potential involvement in l-carnosine supply

Takuya Usui, Yoshiyuki Kubo, Shin Ichi Akanuma, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The supply of l-carnosine, a bioactive dipeptide of β-alanine and l-histidine, to the retina across the blood-retinal barrier (BRB) was studied. The invivo and invitro studies revealed low uptake activities for [3H]Gly-Sar, a representative dipeptide, suggesting that l-carnosine transport plays only a minor role at the BRB. The invivo study using rats showed approximately 18- and 23-fold greater retinal uptake indexes (RUI) for [3H]β-alanine and [3H]l-histidine compared with that of a paracellular marker, respectively. The RUI of [3H]β-alanine was taurine- and γ-aminobutyric acid-sensitive, and the invitro uptake by TR-iBRB2 cells showed time- concentration- and temperature-dependent [3H]β-alanine uptake, suggesting that a carrier-mediated process was involved in β-alanine transport across the inner BRB. [3H]β-Alanine uptake was inhibited by taurine and β-guanidinopropionic acid, suggesting that taurine transporter (TAUT/SLC6A6) is responsible for the influx transport of β-alanine across the inner BRB. Regarding l-histidine, the l-leucine-sensitive RUI of [3H]l-histidine was identified, and the invitro [3H]l-histidine uptake by TR-iBRB2 cells suggested that a carrier-mediated process was involved in l-histidine transport across the inner BRB. The inhibition profile suggested that L-type amino acid transporter (LAT1/SLC7A5) is responsible for the influx transport of l-histidine across the inner BRB. These results show that the influx transports of β-alanine and l-histidine across the inner BRB is carried out by TAUT and LAT1, respectively, suggesting that the retinal l-carnosine is supplied by enzymatic synthesis from two kinds of amino acids transported across the inner BRB.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalExperimental Eye Research
Volume113
DOIs
Publication statusPublished - 2013 Aug
Externally publishedYes

Keywords

  • Dipeptide
  • Inner blood-retinal barrier
  • L-carnosine
  • L-histidine
  • Transporter
  • β-alanine

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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