L-Homocysteic acid
(Synonyms: L-HCA) 目录号 : GC66843
L-Homocysteic acid (L-HCA) 是一种内源性兴奋性氨基酸，可作为 NMDA 受体激动剂 (EC50: 14 μM)。L-Homocysteic acid 具有神经毒性，可用于神经系统疾病的研究。
Cas No.:14857-77-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
L-Homocysteic acid (L-HCA) is an endogenous excitatory amino acid that acts as a NMDA receptor agonist (EC50: 14 μM). L-Homocysteic acid is neurotoxic, and can be used in the research of neurological disorders[1][2][3].
L-Homocysteic acid activates NMDA receptor with an EC50 value of 14 μM[1].
L-Homocysteic acid (100 μM) induces large currents (1.8 nA) that is insensitive to the NMDA receptor-antagonist mixture in Purkinje cells[1].
L-Homocysteic acid (250 μM, 30 min) potently induces an acute excitotoxic reaction in ex vivo chick embryo retina[2].
L-Homocysteic acid (0-2 mM, 48 h) induces a concentration-dependent neurotoxic effect in rat primary neurons[3].
L-Homocysteic acid (intraperitoneal injection, 4-11 mmol/kg) elicits seizures in rats during early postnatal development[4].
L-Homocysteic acid (intraperitoneal injection, 100-1500 mg/kg) partially substitutes for NMDA, producing maximum values of 61-67% NMDA-lever responding at doses of 1000 and 560 mg/kg, respectively in Sprague-Dawley rats[5].
| Animal Model: | Male albino rats of the Wistar strain[4] |
| Dosage: | 4, 5.5, 8, 11 mM/kg |
| Administration: | Intraperitoneal injection, daily for 14 days |
| Result: | Induced flexion seizures at 4 mmol/kg. Led to intense tail flicking, pivoting, and locomotion. Decreased ECoG (electrocorticograms) activity for 5-9 min. |
[1]. M Yuzaki, et al. Characterization of L-homocysteate-induced currents in Purkinje cells from wild-type and NMDA receptor knockout mice. J Neurophysiol . 1999 Nov;82(5):2820-6.
[2]. J W Olney, et al. L-homocysteic acid: an endogenous excitotoxic ligand of the NMDA receptor. Brain Res Bull. 1987 Nov;19(5):597-602.
[3]. B Lockhart, et al. Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers. Brain Res. 2000 Feb 14;855(2):292-7.
[4]. P Mares, et al. Convulsant action of D,L-homocysteic acid and its stereoisomers in immature rats.
[5]. Katherine L Nicholson, et al. The discriminative stimulus effects of N-methyl-D-aspartate glycine-site ligands in NMDA antagonist-trained rats. Psychopharmacology (Berl). 2009 Apr;203(2):441-51.
| Cas No. | 14857-77-3 | SDF | Download SDF |
| 别名 | L-HCA | ||
| 分子式 | C4H9NO5S | 分子量 | 183.18 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.4591 mL | 27.2956 mL | 54.5911 mL |
| 5 mM | 1.0918 mL | 5.4591 mL | 10.9182 mL |
| 10 mM | 0.5459 mL | 2.7296 mL | 5.4591 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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L-Homocysteic acid: an endogenous excitotoxic ligand of the NMDA receptor
Brain Res Bull 1987 Nov;19(5):597-602.PMID:2891418DOI:10.1016/0361-9230(87)90077-3.
L-Homocysteic acid (L-HCA) has been proposed as a natural transmitter at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor based on recent evidence that L-HCA occurs L-HCA occurs naturally in the mammalian CNS, is released from K+ stimulated brain slices in a calcium-dependent manner and may be contained in nerve terminals located in certain brain regions that have a high density of NMDA receptors. Here we report that L-HCA potently induces a pattern of cytopathology in the ex vivo chick retina which mimics the pattern of NMDA but not kainic acid (KA) neurotoxicity. We also show that known NMDA antagonists, including Mg++, D-aminophosphonopentanoate and certain anesthetics, analgesics, and sedative hypnotics block the neurotoxic actions of L-HCA in direct proportion to their efficacy in blocking NMDA neurotoxicity. While there is a perfect correspondence between agents that block NMDA and L-HCA neurotoxicity, only a few such agents are active against KA neurotoxicity. We find that 3H-Glu binding is inhibited more potently by L-HCA (Ki = 67 microM). Moreover the patterns with which L-HCA and NMDA displace 3H-Glu binding in autoradiograms appear essentially identical. These findings are consistent with the proposal that L-HCA is an endogenous ligand at NMDA receptors.
L-Homocysteic acid as an alternative cytotoxin for studying glutamate-induced cellular degeneration of Huntington's disease and normal skin fibroblasts
Life Sci 1985 Oct 21;37(16):1483-9.PMID:2864622DOI:10.1016/0024-3205(85)90179-1.
Huntington's Disease (HD) and normal skin fibroblasts in culture were exposed to several acidic amino acids structurally related to L-glutamate which have excitotoxic properties in the nervous system. L-Homocysteic acid, a sulfonic acid analogue of glutamate, was the only other acidic amino acid causing fibroblast degeneration similar to that induced by glutamate. None of the other compounds tested, including the D isomer of homocysteic acid, were as toxic as 30 mM glutamate. As previously noted with glutamate treatment, HD fibroblasts demonstrated an increased sensitivity to L-Homocysteic acid compared to controls. In contrast to glutamate, no cellular metabolism of L-Homocysteic acid could be detected; a property which may account for the increased cytotoxicity of L-Homocysteic acid compared to glutamate. The identification of L-Homocysteic acid, a glutamate analogue which undergoes limited metabolism, should enable the elucidation of the toxic mechanism of glutamate and facilitate the determination of the site conferring increased sensitivity of cultured HD fibroblasts to glutamate.
Inhibition of L-Homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers
Brain Res 2000 Feb 14;855(2):292-7.PMID:10677603DOI:10.1016/s0006-8993(99)02372-0.
In the present report, we have set out to investigate the potential capacity of both the oxidised and reduced forms of RS-alpha-lipoic acid, and its separate R-(+) and S-(-)enantiomers, to prevent cell death induced with L-Homocysteic acid (L-HCA) and buthionine sulphoximine (BSO) in rat primary cortical and hippocampal neurons. L-HCA induced a concentration-dependent neurotoxic effect, estimated by cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction, in primary neurons, but was significantly more toxic for hippocampal (EC(50)=197 microM) compared with cortical neurons (EC(50)=1016 microM) whereas D-HCA demonstrated only moderate (<20%) toxicity. On the other hand, cortical and hippocampal cultures were equally susceptible (341 and 326 microM, respectively) to the neurotoxic action of BSO. Antioxidants including butylated hydroxyanisole, propyl gallate and vitamin E protected cells against the neurotoxic effect of L-HCA and BSO. However, N-acetyl-cysteine and tert-butylphenyl nitrone, although capable of abrogating L-HCA-mediated cell death showed no protective effect against BSO-mediated toxicity. RS-alpha-lipoic acid, RS-alpha-dihydrolipoic acid and the enantiomers R-alpha-lipoic acid and S-alpha-lipoic acid protected cells against L-HCA-mediated toxicity with EC(50) values between 3.1-8.3 microM in primary hippocampal neurons and 2.6-16.8 microM for cortical neurons. However, RS-alpha-lipoic acid, RS-alpha-dihydrolipoic acid, and S-alpha-lipoic acid failed to protect cells against the degeneration induced by prolonged exposure to BSO, whereas the natural form, R-alpha-lipoic, was partially active under the same conditions. The present results indicate a unique sensitivity of hippocampal neurons to the effect of L-HCA-mediated toxicity, and suggest that RS-alpha-lipoic acid, and in particular the R-alpha-enantiomeric form is capable of preventing oxidative stress-mediated neuronal cell death in primary cell culture.
The lathyrus toxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid
Toxicol Appl Pharmacol 2007 Feb 15;219(1):1-9.PMID:17234231DOI:10.1016/j.taap.2006.11.027.
A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the endogenous compound, L-cystine. This phenomenon has been termed QUIS sensitization. A mechanism similar to that previously described for QUIS neurotoxicity has been proposed to describe QUIS sensitization. Specifically, QUIS has been shown to be sequestered into GABAergic interneurons by the System x(c)(-) and subsequently released by heteroexchange with cystine or L-AP6, resulting in activation of non-NMDA receptors. We now report two additional neurotoxins, the Lathyrus excitotoxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and the endogenous compound, L-Homocysteic acid (HCA), sensitize CA1 hippocampal neurons >50-fold to L-AP6 and >10-fold to cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP- or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA agonist that induces phosphonate or cystine sensitization. Like QUIS sensitization, the sensitization evoked by either ODAP or HCA can be reversed by a subsequent exposure to 2 mM alpha-aminoadipic acid. Finally, we have demonstrated that there is a correlation between the potency of inducers for triggering phosphonate or cystine sensitivity and their affinities for System x(c)(-) and either the non-NMDA or NMDA receptor. Thus, the results of this study support our previous model of QUIS sensitization and have important implications for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.
L-Homocysteic acid selectively activates N-methyl-D-aspartate receptors of rat retinal ganglion cells
Neurosci Lett 1992 May 25;139(2):173-7.PMID:1351663DOI:10.1016/0304-3940(92)90545-i.
To explore the possible role of L-Homocysteic acid (HCA) as a retinal transmitter, whole-cell recordings with patch electrodes were performed on isolated rat retinal ganglion cells (RGCs) in culture. HCA elicited an inward current at -60 mV. Similar to currents evoked at this potential in RGCs by N-methyl-D-aspartate (NMDA), HCA-activated currents were of relatively small amplitude (10-150 pA), and the noise level increased dramatically during the response. When HCA was co-applied with concentrations of NMDA that elicited a maximal response, the current was not increased over that of NMDA alone. HCA-evoked currents were almost completely blocked by the NMDA antagonists D-2-amino-5-phosphonovalerate (D-AP5), Mg2+, or 7-chlorokynurenate (7-Cl KYN). Unlike its effects on other preparations, even millimolar concentrations of HCA did not activate kainate-like currents. These observations suggest that HCA specifically activates the NMDA receptor-channel complex of rat RGCs.