TY - JOUR
T1 - β-Alanine and l-histidine transport across the inner blood-retinal barrier
T2 - Potential involvement in l-carnosine supply
AU - Usui, Takuya
AU - Kubo, Yoshiyuki
AU - Akanuma, Shin Ichi
AU - Hosoya, Ken Ichi
N1 - Funding Information:
The present study was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) , Suzuken Memorial Foundation (Nagoya, Japan) .
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Dipeptide
KW - Inner blood-retinal barrier
KW - L-carnosine
KW - L-histidine
KW - Transporter
KW - β-alanine
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U2 - 10.1016/j.exer.2013.06.002
DO - 10.1016/j.exer.2013.06.002
M3 - Article
C2 - 23773890
AN - SCOPUS:84879732750
VL - 113
SP - 135
EP - 142
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
ER -