Hypertonicity Enhances GABA Uptake by Cultured Rat Retinal Capillary Endothelial Cells

Abstract

We have reported previously that taurine transporter (TauT) mediates γ-aminobutyric acid (GABA) as a substrate in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells). This study investigates how TauT-mediated GABA transport is regulated in TR-iBRB2 cells under hypertonic conditions. [³H]GABA uptake by TR-iBRB2 cells exposed to 12 h- to 24 h-hypertonic culture medium was significantly greater than that of isotonic culture medium. [³H]GABA uptake by TR-iBRB2 cells was Na(+)-, Cl(-)-, and concentration-dependent with a Michaelis-Menten (K(m)) constant of 3.5 mM under isotonic conditions and K(m) of 0.324 and 5.48 mM under hypertonic conditions. Under hypertonic conditions, [³H]GABA uptake by TR-iBRB2 cells was more potently inhibited by substrates of TauT, such as taurine and β-alanine, than those of GABA transporters such as GABA, nipecotic acid, and betaine. These results suggest that an unknown high-affinity GABA transport process and TauT-mediated GABA transport are enhanced under hypertonic conditions. In conclusion, hypertonicity enhances GABA uptake by cultured rat retinal capillary endothelial cells.

Roles of Drug Transporters in Blood-Retinal Barrier

“…TAUT also mediates transport of β-alanine and gamma-aminobutyric acid (GABA) (Tomi et al 2008;Usui et al 2013). Hyperosmolar conditions could stimulate activity of TAUT, leading to increase in V max of taurine without affecting K m (El-Sherbeny et al 2004;Yahara et al 2010). Both in vivo and in vitro data demonstrated that taurine itself enhanced expression of retinal TAUT (Zeng et al 2010).…”