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(RS)-3,5-DHPG Sale

(Synonyms: (RS)-3,5-二羟基苯甘氨酸,DHPG) 目录号 : GC15342

An agonist of group I mGluRs

(RS)-3,5-DHPG Chemical Structure

Cas No.:19641-83-9

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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Cell experiment [1]:

Cell lines

MÜller cell

Preparation Method

(RS)-3,5-DHPG treatment induced the purification of cultured rat retinal Muller cells.

Reaction Conditions

(RS)-3,5-DHPG (10 µM) for 0.5-24 h.

Applications

(RS)-3,5-DHPG treatment induced down-regulation of Kir4.1 protein in cell membrane compartments of Muller cells.

Animal experiment [2]:

Animal models

Adult male Sprague Dawley rats (250-280 g)

Preparation Method

To determine mechanisms underlying the effects of (RS)-3,5-DHPG infusion, some animals received two consecutive infusions conducted 10 min apart. Rats in these groups received infusions of ACSF followed by ACSF, ACSF followed by (RS)-3,5-DHPG (50 µmol), ACSF followed by the group I mGluR antagonist MPEP, or MPEP followed by (RS)-3,5-DHPG (50 µmol), ACSF followed by the PKD1 inhibitor followed by (RS)-3,5-DHPG (50 µmol).

Dosage form

50 µmol (RS)-3,5-DHPG for 5 days

Applications

Impairments of spatial memory induced by bilateral infusions of (RS)-3,5-DHPG (50 µmol) into the CA1 area. Dose-dependent changes in spatial memory induced by (RS)-3,5-DHPG infusion. Pre-infusion of MPEP or CID755673 prevented impairments of spatial memory induced by (RS)-3,5-DHPG infusion.

References:

[1]. Gao F, Li F, et,al. Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal MÜller cells. Neurosci Lett. 2015 Feb 19;588:12-7. doi: 10.1016/j.neulet.2014.12.048. Epub 2014 Dec 27. PMID: 25549543.
[2]. Wang W, Duclot F, et,al. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.

产品描述

DHPG ((RS)-3,5-DHPG) is an amino acid that is a selective potent agonist for group I mGluR (mGluR 1 and mGluR 5) and has no effect on Group II and III mGluR [1,6]. DHPG ((RS)-3,5-DHPG) is also a potent antagonist of mGluRs associated with phospholipase D[2].

(RS)-3,5-DHPG (10μM) treatment induced Müller cell gliosis, as evidenced by enhanced GFAP expression. In addition, (RS)-3,5-DHPG (10 and 100μM) treatment induced a transient decrease in Kir4.1 mRNA expression in the cells. Activation of mGluR I by (RS)-3,5-DHPG may decrease the number of functional Kir4.1 channels in purified cultured rat retinal Müller cells through modulating Kir4.1 protein and mRNA, thus contributing to Müller cell gliosis[5].

Impairments of spatial memory induced by bilateral infusions of (RS)-3,5-DHPG (50 μmol) into the CA1 area. Dose-dependent changes in spatial memory induced by (RS)-3,5-DHPG infusion. Pre-infusion of MPEP or CID755673 prevented impairments of spatial memory induced by (RS)-3,5-DHPG infusion[3]. Hippocampal GPR30 expression was reduced in middle-aged mice compared with young adult mice. a group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-DHPG -induced long-term depression in mossy fiber-cornu ammonis 3 (MF-CA3) synapses but not SC-CA1 synapses was facilitated in brain slices from G1-treated middle-aged mice[4]. (RS)-3,5-DHPG elicited acute mechanical allodynia and thermal hyperalgesia in na?ve mice from 1 h to 12 h following intrathecal (central/spinal) administration.The attenuation of intrathecal (RS)-3,5-DHPG -evoked acute pain by artesunate therapy in rats[7].

References:
[1]: Winder DG, Conn PJ. Metabotropic glutamate receptor (mGluR)-mediated potentiation of cyclic AMP responses does not require phosphoinositide hydrolysis: mediation by a group II-like mGluR. J Neurochem. 1995 Feb;64(2):592-9. doi: 10.1046/j.1471-4159.1995.64020592.x. PMID: 7830052.
[2]: Pellegrini-Giampietro DE, Torregrossa SA, Moroni F. Pharmacological characterization of metabotropic glutamate receptors coupled to phospholipase D in the rat hippocampus. Br J Pharmacol. 1996 Jun;118(4):1035-43. doi: 10.1111/j.1476-5381.1996.tb15503.x. PMID: 8799579; PMCID: PMC1909512.
[3]: Wang W, Duclot F, et,al. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.
[4]: Xu W, Cao J, et,al. GPR30 activation improves memory and facilitates DHPG-induced LTD in the hippocampal CA3 of middle-aged mice. Neurobiol Learn Mem. 2018 Mar;149:10-19. doi: 10.1016/j.nlm.2018.02.005. Epub 2018 Feb 6. PMID: 29421611.
[5]: Gao F, Li F, et,al. Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Müller cells. Neurosci Lett. 2015 Feb 19;588:12-7. doi: 10.1016/j.neulet.2014.12.048. Epub 2014 Dec 27. PMID: 25549543.
[6]: Ito I, Kohda A, et,al. 3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors. Neuroreport. 1992 Nov;3(11):1013-6. PMID: 1362358.
[7]: Zhang L, Zhao Y, et,al.Artesunate Reduces Remifentanil-induced Hyperalgesia and Peroxiredoxin-3 Hyperacetylation via Modulating Spinal Metabotropic Glutamate Receptor 5 in Rats. Neuroscience. 2022 Apr 1;487:88-98. doi: 10.1016/j.neuroscience.2022.01.003. Epub 2022 Jan 11. PMID: 35026318.

DHPG ((RS)-3,5-DHPG) 是一种氨基酸,是 I 组 mGluR(mGluR 1 和 mGluR 5)的选择性强效激动剂,对 II 组和 III 组 mGluR 没有影响 [ 1,6]。 DHPG ((RS)-3,5-DHPG) 也是与磷脂酶 D[2] 相关的 mGluRs 的有效拮抗剂。

(RS)-3,5-DHPG (10μM) 处理可诱导 MÜller 细胞神经胶质增生,增强的 GFAP 表达证明了这一点。此外,(RS)-3,5-DHPG(10 和 100μM)处理诱导细胞中 Kir4.1 mRNA 表达的瞬时降低。 (RS)-3,5-DHPG 激活 mGluR I 可能通过调节 Kir4.1 蛋白和 mRNA 减少纯化培养的大鼠视网膜 MÜller 细胞中功能性 Kir4.1 通道的数量,从而促进 MÜller 细胞神经胶质增生[ 5].

向 CA1 区域双侧输注 (RS)-3,5-DHPG (50 μmol) 会导致空间记忆受损。 (RS)-3,5-DHPG 输注引起的空间记忆的剂量依赖性变化。预输注 MPEP 或 CID755673 可防止 (RS)-3,5-DHPG 输注引起的空间记忆损伤[3]。与年轻的成年小鼠相比,中年小鼠的海马 GPR30 表达降低。 I 组代谢型谷氨酸受体 (mGluR) 激动剂 (RS)-3,5-DHPG 在苔藓纤维-角氨 3 (MF-CA3) 突触中诱导长期抑制,但在脑切片中促进了 SC-CA1 突触G1处理的中年小鼠[4]。 (RS)-3,5-DHPG 在鞘内(中央/脊髓)给药后 1 小时至 12 小时内在幼稚小鼠中引起急性机械异常性疼痛和热痛觉过敏。鞘内(RS)-3,5-DHPG 诱发的急性青蒿琥酯治疗大鼠的疼痛[7].

Chemical Properties

Cas No. 19641-83-9 SDF
别名 (RS)-3,5-二羟基苯甘氨酸,DHPG
化学名 2-amino-2-(3,5-dihydroxyphenyl)acetic acid
Canonical SMILES NC(C(O)=O)C1=CC(O)=CC(O)=C1
分子式 C8H9NO4 分子量 183.16
溶解度 DMSO : 5 mg/mL (27.30 mM; ultrasonic and warming and heat to 60°C); <1.83mg/ml in Water 储存条件 4°C, stored under nitrogen
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Research Update

Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats

PLoS One2018 Apr 3;13(4):e0195095.PMID: 29614089DOI: 10.1371/journal.pone.0195095

Background: Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation of group I mGluRs (mGluR1 and mGluR5) in cultured hippocampal neurons by application of (S)-3,5-Dihydroxyphenylglycine (DHPG) causes the regulated internalization of N-methyl-D-aspartate receptors (NMDARs), which subsequently activates protein kinase D1 (PKD1). Through phosphorylating the C-terminals of the NMDAR GluN2 subunits, PKD1 down-regulates the activity of remaining (non-internalized) surface NMDARs. The knockdown of PKD1 does not affect the DHPG-induced inhibition of AMPA receptor-mediated miniature excitatory post-synaptic currents (mEPSCs) but prevents the DHPG-induced inhibition of NMDAR-mediated mEPSCs in vitro. Thus, we investigated the in vivo effects of bilateral infusions of DHPG into the hippocampal CA1 area of rats in the Morris water maze (MWM) and the novel object discrimination (NOD) tests. Methods: A total of 300 adult male Sprague Dawley rats (250-280 g) were used for behavioral tests. One hundred ninety four were used in MWM test and the other 106 rats in the NOD test. Following one week of habituation to the vivarium, rats were bilaterally implanted under deep anesthesia with cannulas aimed at the CA1 area of the hippocampus (CA1 coordinates in mm from Bregma: AP -3.14; lateral +/-2; DV -3.0). Through implanted cannulas artificial cerebrospinal fluid (ACSF), the group1 mGluR antagonist 6-Methyl-2-(phenylethynyl)pyridine (MPEP), the dynamin-dependent internalization inhibitor Dynasore, or the PKD1 inhibitor CID755673 were infused into the bilateral hippocampal CA1 areas (2 per side, over 5 min). The effects of these infusions and the effects of PKD1 knockdown were examined in MWM or NOD test. Results: DHPG infusion increased the latency to reach the platform in the MWM test and reduced the preference for the novel object in the NOD task. We found that the DHPG effects were dose-dependent and could be maintained for up to 2 days. Notably, these effects could be prevented by pre-infusion of the group1 mGluR antagonist MPEP, the dynamin-dependent internalization inhibitor Dynasore, the PKD1 inhibitor CID755673, or by PKD1 knockdown in the hippocampal CA1 area. Conclusion: Altogether, these findings provide direct evidence that PKD1-mediated signaling may play a critical role in the induction of learning and memory impairments by DHPG infusion into the hippocampal CA1 area.

DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists

Neuropharmacology1999 Oct;38(10):1577-83.PMID: 10530819DOI: 10.1016/s0028-3908(99)00123-9

We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CA1 region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu5 selective agonist 2-chloro-5-hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu1 and mGlu5 receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu1 selective antagonist (S)-2-methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu5 receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD.

DHPG activation of group 1 mGluRs in BLA enhances fear conditioning

Learn Mem2009 Jun 24;16(7):421-5.PMID: 19553379DOI: 10.1101/lm.1444909

Group 1 metabotropic glutamate receptors are known to play an important role in both synaptic plasticity and memory. We show that activating these receptors prior to fear conditioning by infusing the group 1 mGluR agonist, (R.S.)-3,5-dihydroxyphenylglycine (DHPG), into the basolateral region of the amygdala (BLA) of adult Sprague-Dawley rats enhances freezing normally supported by a weak footshock. This effect of DHPG was blocked when it was co-infused with either the general group 1 mGluR1 antagonist, (R,S)-1-aminoindan-1,5 dicarboxylic acid (AIDA), or with the selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP). These results support previous findings by Rodrigues and colleagues that mGluR5s in the lateral region of the amygdala make an import contribution to fear conditioning. More importantly, they support the general ideas embedded in the concept of metaplasticity, as per Abraham, and the synaptic-tagging hypothesis per Frey and Morris-that the processes that specify the content of experience can be experimentally separated from those needed to acquire the memory.

GPR30 activation improves memory and facilitates DHPG-induced LTD in the hippocampal CA3 of middle-aged mice

Neurobiol Learn Mem2018 Mar;149:10-19.PMID: 29421611DOI: 10.1016/j.nlm.2018.02.005

Reduced estrogen levels and decreased expression of related receptors are typical cerebral features of aging. The G protein-coupled estrogen receptor 1 (GPER1, also known as GPR30) is considered a novel therapeutic target for neurodegenerative diseases. In this study, we demonstrated that hippocampal GPR30 expression was reduced in middle-aged mice compared with young adult mice. GPR30 agonist G1 improved both fear and spatial memory in both male and female middle-aged mice, but not in young adult mice, which were blocked by the GPR30 antagonist G15. Interestingly, a group I metabotropic glutamate receptor (mGluR) agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced long-term depression (LTD) in mossy fiber-cornu ammonis 3 (MF-CA3) synapses but not Schaffer collateral-CA1 (SC-CA1) synapses was facilitated in brain slices from G1-treated middle-aged mice. Long-term potentiation (LTP) in SC-CA1 synapses was not affected in slices from G1-treated mice. The effects of GPR30 activation on memory and DHPG-LTD in MF-CA3 synapses were further confirmed by viral expression of GPR30 in the CA3. The regulation of hippocampal synaptic plasticity by G1 treatment might be related to brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling, as G15 also blocked G1-induced activation of the BDNF-TrkB pathway. Moreover, we found that DHPG triggered GluA internalization in slices from G1-treated mice but not control mice. Pharmacological experiments showed that G1-mediated facilitation of DHPG-induced LTD in MF-CA3 synapses was dependent on protein kinase B (Akt), mammalian target of rapamycin (mTor), and TrkB signaling. In conclusion, our results indicate that GPR30 activation improves memory in middle-aged mice, likely through facilitating synaptic plasticity in the CA3. This study provides novel evidence that GPR30 activation can improve memory in middle-aged animals.

Antisense oligonucleotide against GTPase Rab5b inhibits metabotropic agonist DHPG-induced neuroprotection

Brain Res2004 Nov 26;1028(1):59-65.PMID: 15518642DOI: 10.1016/j.brainres.2004.08.064

(S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR1 and 5) agonist reduced NMDA-mediated membrane currents, NMDA-induced cell death and up-regulated Rab5b, a small GTPase involved in endocytosis [M. Blaabjerg, A. Baskys, J. Zimmer and M. P. Vawter, Changes in hippocampal gene expression after neuroprotective activation of group I metabotropic glutamate receptors, Molec. Brain Res. 117 (2003) 196-205; M. Blaabjerg, L. Fang, J. Zimmer and A. Baskys, Neuroprotection against NMDA excitotoxicity by group I metabotropic glutamate receptors is associated with reduction of NMDA stimulated currents, Experimental Neurol. 183 (2003) 573-580.]. To examine the role of Rab5b on DHPG-mediated neuroprotection in organotypic hippocampal cultures, we developed antisense oligonucleotide targeted to suppress Rab5b translation. Treatment of cultures with the antisense (24 h) but not scrambled sequence oligonucleotide suppressed DHPG-induced increase in Rab5b expression and significantly disrupted DHPG-induced protection against NMDA toxicity in a concentration-dependent manner (0.01-10 nM). Antisense but not scrambled oligonucleotide treatment reduced NMDA toxicity (to 74.4+/-5.9% of control) and this effect could be blocked by protein kinase C inhibitor staurosporine (0.2 microM) or with the protease inhibitor leupeptin (100 microM). Application of osmotic shock followed by K(+) depletion to disrupt endocytosis abolished the protective effect of DHPG. These data suggest that neuroprotection by DHPG against NMDA-mediated injury may involve facilitation of NMDA receptor endocytosis likely stimulated by DHPG-induced increase in Rab5b synthesis.