L-(-)-threo-3-Hydroxyaspartic acid is a naturally occurring amino acid derivative with a specific stereochemical configuration. L-(-)-threo-3-Hydroxyaspartic acid is a selective agonist for glutamate receptors, particularly the NMDA receptor[1-2]. L-(-)-threo-3-Hydroxyaspartic acid is primarily used in neuroscience research as a tool compound for studying glutamatergic neurotransmission and receptor pharmacology[3-4].
In vitro, when Xenopus oocytes expressing EAAT4 were incubated with L-(-)-threo-3-Hydroxyaspartic acid (100μM). L-(-)-threo-3-Hydroxyaspartic acid competed with L-aspartate for binding to EAAT4 and induced an inward current[5]. L-(-)-threo-3-Hydroxyaspartic acid (100μM) was directly applied to migrating human U87MG glioma cells on Matrigel for 15 minutes. L-(-)-threo-3-Hydroxyaspartic acid increased the oscillation frequency of cells with spontaneous calcium oscillations and induced calcium oscillations in previously quiescent cells[6].
In vivo, L-(-)-threo-3-Hydroxyaspartic acid (833μM; 0.3±0.1µl) was locally injected into the substantia nigra pars compacta of rats three times a week for three weeks (a total of 9 injections). L-(-)-threo-3-Hydroxyaspartic acid resulting in morphological damage to neurons in the substantia nigra pars compacta[7]. L-(-)-threo-3-Hydroxyaspartic acid (100μM) was locally applied via pressure ejection (50ms pulses) from a glass micropipette near parenchymal arterioles in the somatosensory cortex of anesthetized C57BL/6J mice while monitoring changes in vascular diameter. L-(-)-threo-3-Hydroxyaspartic acid significantly increased arteriole diameter, mimicking the neurovascular coupling response[8].
References:
[1] Hara R, Nakano M, Kino K. One-Pot Production of L-threo-3-Hydroxyaspartic Acid Using Asparaginase-Deficient Escherichia coli Expressing Asparagine Hydroxylase of Streptomyces coelicolor A3(2). Appl Environ Microbiol. 2015 Jun;81(11):3648-54.
[2] Munir M, Correale DM, Robinson MB. Substrate-induced up-regulation of Na(+)-dependent glutamate transport activity. Neurochem Int. 2000 Aug-Sep;37(2-3):147-62.
[3] Jensen AA, Bräuner-Osborne H. Pharmacological characterization of human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 in a fluorescence-based membrane potential assay. Biochem Pharmacol. 2004 Jun 1;67(11):2115-27.
[4] Wang Z, Li W, Mitchell CK, et al. Activation of protein kinase C reduces GLAST in the plasma membrane of rat Müller cells in primary culture. Vis Neurosci. 2003 Nov-Dec;20(6):611-9.
[5] Shigeri Y, Shimamoto K, Yasuda-Kamatani Y, et al. Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5). J Neurochem. 2001 Oct;79(2):297-302.
[6] Hamadi A, Giannone G, Takeda K, et al. Glutamate involvement in calcium-dependent migration of astrocytoma cells. Cancer Cell Int. 2014 May 19;14:42.
[7] Loopuijt LD. Local application of L- threo-hydroxyaspartate and malonate in rats in vivo induces rigidity and damages neurons of the substantia nigra, pars compacta. J Neural Transm (Vienna). 2002 Oct;109(10):1275-94.
[8] Jackson JG, Krizman E, Takano H, et al, Activation of Glutamate Transport Increases Arteriole Diameter in vivo: Implications for Neurovascular Coupling. Front Cell Neurosci. 2022 Mar 4;16:831061.
L-(-)-threo-3-Hydroxyaspartic acid 是一种天然存在的、具有特定立体化学构型的氨基酸衍生物。L-(-)-threo-3-Hydroxyaspartic acid是谷氨酸受体（特别是NMDA受体）的一种选择性激动剂[1-2]。L-(-)-threo-3-Hydroxyaspartic acid主要用于神经科学研究，作为研究谷氨酸能神经传递和受体药理学的工具化合物[3-4]。
在体外，在L-(-)-threo-3-Hydroxyaspartic acid（100μM）孵育表达EAAT4的卵母细胞时。L-(-)-threo-3-Hydroxyaspartic acid与L-天冬氨酸竞争结合EAAT4，可诱导内向电流[5]。L-(-)-threo-3-Hydroxyaspartic acid（100μM）直接处理在基质胶上迁移的人U87MG胶质瘤细胞15分钟。L-(-)-threo-3-Hydroxyaspartic acid能够增加具有自发性钙振荡细胞的振荡频率，并诱导原本静止的细胞产生钙振荡[6]。
在体内，L-(-)-threo-3-Hydroxyaspartic acid（833μM；0.3±0.1µl）局部注射至大鼠黑质致密部，每周三次，持续三周（共9次注射），可导致大鼠黑质致密部神经元的形态学损伤[7]。L-(-)-threo-3-Hydroxyaspartic acid（100μM）通过玻璃微管局部压力注射（50ms脉冲），应用于麻醉的C57BL/6J小鼠体感皮层小动脉附近，同时监测血管直径变化。L-(-)-threo-3-Hydroxyaspartic acid显著增加了小动脉直径，模拟了神经血管耦合反应[8]。