TY - JOUR
T1 - Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells
AU - Tomi, Masatoshi
AU - Tajima, Ayumi
AU - Tachikawa, Masanori
AU - Hosoya, Ken ichi
N1 - Funding Information:
This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and a grant for Research on Sensory and Communicative Disorders by the Ministry of Health, Labor, and Welfare, Japan.
PY - 2008/10
Y1 - 2008/10
N2 - The purpose of this study was to identify the uptake mechanism of γ-aminobutyric acid (GABA) via taurine transporter (Slc6a6/TauT) and its relationship with GABA transport at the inner BRB. Rat Slc6a6/TauT-transfected HeLa cells exhibited Na+-, Cl--, and concentration-dependent [3H]GABA uptake with a Km of 1.5 mM. Taurine, β-alanine, and GABA markedly inhibited Slc6a6/TauT-mediated uptake of [3H]GABA. The uptake of [3H]GABA by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) was Na+-, Cl--, and concentration-dependent with a Km of 2.0 mM. This process was more potently inhibited by substrates of Slc6a6/TauT, taurine and β-alanine, than those of GABA transporters, GABA and betaine. In the presence of taurine, there was competitive inhibition with a Ki of 74 μM. [3H]Taurine also exhibited competitive inhibition with a Ki of 1.8 mM in the presence of GABA. In conclusion, rat Slc6a6/TauT has the ability to use GABA as a substrate and Slc6a6/TauT-mediated GABA transport appears to be present at the inner BRB.
AB - The purpose of this study was to identify the uptake mechanism of γ-aminobutyric acid (GABA) via taurine transporter (Slc6a6/TauT) and its relationship with GABA transport at the inner BRB. Rat Slc6a6/TauT-transfected HeLa cells exhibited Na+-, Cl--, and concentration-dependent [3H]GABA uptake with a Km of 1.5 mM. Taurine, β-alanine, and GABA markedly inhibited Slc6a6/TauT-mediated uptake of [3H]GABA. The uptake of [3H]GABA by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) was Na+-, Cl--, and concentration-dependent with a Km of 2.0 mM. This process was more potently inhibited by substrates of Slc6a6/TauT, taurine and β-alanine, than those of GABA transporters, GABA and betaine. In the presence of taurine, there was competitive inhibition with a Ki of 74 μM. [3H]Taurine also exhibited competitive inhibition with a Ki of 1.8 mM in the presence of GABA. In conclusion, rat Slc6a6/TauT has the ability to use GABA as a substrate and Slc6a6/TauT-mediated GABA transport appears to be present at the inner BRB.
KW - Blood-retinal barrier
KW - Carrier-mediated transport
KW - Retinal capillary endothelial cell
KW - Taurine transporter
KW - γ-Aminobutyric acid
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U2 - 10.1016/j.bbamem.2008.04.012
DO - 10.1016/j.bbamem.2008.04.012
M3 - Article
C2 - 18501699
AN - SCOPUS:52049118519
SN - 0005-2736
VL - 1778
SP - 2138
EP - 2142
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 10
ER -