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dl-threo-β-Benzyloxyaspartate, A PotentBlocker of ExcitatoryAmino AcidTransporters Keiko ShimamotoBruno LebrunYoshimi Yasuda‐Kamatani1998 год

dl-threo-β-Benzyloxyaspartate, A Potent Blocker of Excitatory Amino Acid Transporters
статья из журнала

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Аннотация: DL-threo-beta-Benzyloxyaspartate (DL-TBOA), a novel derivative of DL-threo-beta-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) (Ki = 42 microM) with almost the same potency as DL-threo-beta-hydroxyaspartate (Ki = 58 microM). With regard to the human excitatory amino acid transporter-2 (EAAT2), the inhibitory effect of DL-TBOA (Ki = 5.7 microM) was much more potent than that of dihydrokainate (Ki = 79 microM), 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 adding DL-TBOA without a significant change in the maximum current. The Kb values for human EAAT1 and EAAT2 expressed in X. laevis oocytes were 9.0 microM 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.
Год издания: 1998
Авторы: Keiko Shimamoto, Bruno Lebrun, Yoshimi Yasuda‐Kamatani, Masahiro Sakaitani, Yasushi Shigeri, Noboru Yumoto, Terumi Nakajima
Издательство: American Society for Pharmacology and Experimental Therapeutics
Источник: Molecular Pharmacology
Ключевые слова: Neuroscience and Neuropharmacology Research, Receptor Mechanisms and Signaling, Ion channel regulation and function
Другие ссылки: Molecular Pharmacology (HTML)
PubMed (HTML)