title: Β-alanine and l-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply.
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 in vivo and in vitro studies revealed low uptake activities for [(3)H]Gly-Sar, a representative dipeptide, suggesting that l-carnosine transport plays only a minor role at the BRB. The in vivo study using rats showed approximately 18- and 23-fold greater retinal uptake indexes (RUI) for [(3)H]β-alanine and [(3)H]l-histidine compared with that of a paracellular marker, respectively. The RUI of [(3)H]β-alanine was taurine- and γ-aminobutyric acid-sensitive, and the in vitro uptake by TR-iBRB2 cells showed time- concentration- and temperature-dependent [(3)H]β-alanine uptake, suggesting that a carrier-mediated process was involved in β-alanine transport across the inner BRB. [(3)H]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 [(3)H]l-histidine was identified, and the in vitro [(3)H]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.
authors.affiliation: Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Usui
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kubo
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akanuma
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hosoya
mesh_terms: D000818:Animals; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002336:Carnosine / Q000502:physiology*; D002478:Cells, Cultured; D004151:Dipeptides / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D006639:Histidine / Q000378:metabolism*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012171:Retinal Vessels / Q000166:cytology; D013654:Taurine / Q000494:pharmacology; D015091:beta-Alanine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology; D000099247:Taurine Transporters
chemical_list: D002336:Carnosine; D004151:Dipeptides; D006146:Guanidines; D006639:Histidine; D027283:Large Neutral Amino Acid-Transporter 1; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D011422:Propionates; D013654:Taurine; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid; D000099247:Taurine Transporters; C004194:glycylsarcosine; C005775:guanidinopropionic acid
keywords: dipeptide; inner blood-retinal barrier; l-carnosine; l-histidine; transporter; β-alanine