PT  - JOURNAL ARTICLE
AU  - Keiko Shimamoto
AU  - Bruno Lebrun
AU  - Yoshimi Yasuda-Kamatani
AU  - Masahiro Sakaitani
AU  - Yasushi Shigeri
AU  - Noboru Yumoto
AU  - Terumi Nakajima
TI  - <span class="sc">dl</span>-<em>threo</em>-β-Benzyloxyaspartate, A Potent Blocker of Excitatory Amino Acid Transporters
AID  - 10.1124/mol.53.2.195
DP  - 1998 Feb 01
TA  - Molecular Pharmacology
PG  - 195--201
VI  - 53
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/53/2/195.short
4100  - http://molpharm.aspetjournals.org/content/53/2/195.full
SO  - Mol Pharmacol1998 Feb 01; 53
AB  - dl-threo-β-Benzyloxyaspartate (dl-TBOA), a novel derivative ofdl-threo-β-hydroxyaspartate, was synthesized and examined as an inhibitor of sodium-dependent glutamate/aspartate (excitatory amino acid) transporters.dl-TBOA inhibited the uptake of [14C]glutamate in COS-1 cells expressing the human excitatory amino acid transporter-1 (EAAT1) (K i = 42 μm) with almost the same potency asdl-threo-β-hydroxyaspartate (K i = 58 μm). With regard to the human excitatory amino acid transporter-2 (EAAT2), the inhibitory effect of dl-TBOA (K i = 5.7 μm) was much more potent than that of dihydrokainate (K i = 79 μm), which is well known as a selective blocker of this subtype. Electrophysiologically, dl-TBOA induced no detectable inward currents in Xenopus laevis oocytes expressing human EAAT1 or EAAT2. However, it significantly reduced the glutamate-induced currents, indicating the prevention of transport. The dose-response curve of glutamate was shifted by addingdl-TBOA without a significant change in the maximum current. The K b values for human EAAT1 and EAAT2 expressed in X. laevis oocytes were 9.0 μm and 116 nm, respectively. These results demonstrated that dl-TBOA is, so far, the most potent competitive blocker of glutamate transporters.dl-TBOA did not show any significant effects on either the ionotropic or metabotropic glutamate receptors. Moreover,dl-TBOA is chemically much more stable than its benzoyl analog, a previously reported blocker of excitatory amino acid transporters; therefore, dl-TBOA should be a useful tool for investigating the physiological roles of transporters.