2-Linoleoyl Glycerol
(Synonyms: 2LG) 目录号 : GC40400A congener of 2-arachidonoyl glycerol
Cas No.:3443-82-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
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2-Arachidonoyl glycerol (2-AG) has been isolated from porcine brain, and has been characterized as the natural endocannabinoid ligand for the CB1 receptor. The congener of 2-AG in which a linoleoyl group replaces the arachidonoyl group is 2-linoleoyl glycerol (2-LG), and this compound also appears in vivo in conjunction with 2-AG. Although the intrinsic activity of 2-LG is low, it potentiates the activity of other endocannabinoids, including 2-AG. This "entourage" effect has been attributed to blockade of the breakdown and reuptake pathways that normally function to reduce endocannabinoid levels rapidly upon release.
| Cas No. | 3443-82-1 | SDF | |
| 别名 | 2LG | ||
| Canonical SMILES | CCCCC/C=C\C/C=C\CCCCCCCC(=O)OC(CO)CO | ||
| 分子式 | C21H38O4 | 分子量 | 354.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 25 mg/ml,PBS (pH 7.2): 140 µ g/ml | 储存条件 | -80°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 | 2.8209 mL | 14.1044 mL | 28.2087 mL |
| 5 mM | 0.5642 mL | 2.8209 mL | 5.6417 mL |
| 10 mM | 0.2821 mL | 1.4104 mL | 2.8209 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Genetic Manipulation of sn-1-Diacylglycerol Lipase and CB1 Cannabinoid Receptor Gain-of-Function Uncover Neuronal 2-Linoleoyl Glycerol Signaling in Drosophila melanogaster
Cannabis Cannabinoid Res 2021 Apr 15;6(2):119-136.PMID:33912677DOI:10.1089/can.2020.0010.
Introduction: In mammals, sn-1-diacylglycerol lipases (DAGL) generate 2-arachidonoylglycerol (2-AG) that, as the major endocannabinoid, modulates synaptic neurotransmission by acting on CB1 cannabinoid receptors (CB1R). Even though the insect genome codes for inaE, which is a DAGL ortholog (dDAGL), its products and their functions remain unknown particularly because insects lack chordate-type cannabinoid receptors. Materials and Methods: Gain-of-function and loss-of-function genetic manipulations were carried out in Drosophila melanogaster, including the generation of both dDAGL-deficient and mammalian CB1R-overexpressing flies. Neuroanatomy, dietary manipulations coupled with targeted mass spectrometry determination of arachidonic acid and 2-Linoleoyl Glycerol (2-LG) production, behavioral assays, and signal transduction profiling for Akt and Erk kinases were employed. Findings from Drosophilae were validated by a CB1R-binding assay for 2-LG in mammalian cortical homogenates with functionality confirmed in neurons using high-throughput real-time imaging in vitro. Results: In this study, we show that dDAGL is primarily expressed in the brain and nerve cord of Drosophila during larval development and in adult with 2-LG being its chief product as defined by dietary precursor availability. Overexpression of the human CB1R in the ventral nerve cord compromised the mobility of adult Drosophilae. The causality of 2-LG signaling to CB1R-induced behavioral impairments was shown by inaE inactivation normalizing defunct motor coordination. The 2-LG-induced activation of transgenic CB1Rs affected both Akt and Erk kinase cascades by paradoxical signaling. Data from Drosophila models were substantiated by showing 2-LG-mediated displacement of [3H]CP 55,940 in mouse cortical homogenates and reduced neurite extension and growth cone collapsing responses in cultured mouse neurons. Conclusions: Overall, these results suggest that 2-LG is an endocannabinoid-like signal lipid produced by dDAGL in Drosophila.
The Endocannabinoid Analgesic Entourage Effect: Investigations in Cultured DRG Neurons
J Pain Res 2022 Nov 4;15:3493-3507.PMID:36394060DOI:10.2147/JPR.S378876.
Background: The endocannabinoid 2-Arachidonyl glycerol (2-AG) exerts dose-related anti-nociceptive effects, which are potentiated by the related but inactive 2-palmitoyl glycerol (2-PG) and 2-Linoleoyl Glycerol (2-LG). This potentiation of analgesia and other in vivo measures was described as the "entourage effect". We investigated this effect on TRPV1 signalling in cultured dorsal root ganglion (DRG) nociceptors. Methods: Adult rat DRG neurons were cultured in medium containing NGF and GDNF at 37°C. 48 h later cultures were loaded with 2 µM Fura2AM for calcium imaging, and treated with 2-AG, 2-PG and 2-LG, individually or combined, for 5 min, followed by 1 µMol capsaicin. The amplitude and latency of capsaicin responses were measured (N=3-7 rats, controls N=16), and analysed. Results: In controls, 1 µMol capsaicin elicited immediate calcium influx in a subset of neurons, with average latency of 1.27 ± 0.2 s and amplitude of 0.15 ± 0.01 Units. 2-AG (10-100 µMol) elicited calcium influx in some neurons. In the presence of 2-AG (0.001-100 µMol), capsaicin responses were markedly delayed in 64% neurons by up to 320 s (P<0.001). 2-PG increased capsaicin response latency at 0.1 nMol-100 µMol (P<0.001), in 60% neurons, as did 2-LG at 0.1-100 µMol (P<0.001), in 76% neurons. Increased capsaicin response latency due to 2-AG and 2-PG was sensitive to the CB2 but not to the CB1 receptor antagonist. Combined application of 1 µMol 2-AG, 5 µMol 2-PG and 10 µMol 2-LG, also resulted in significantly increased capsaicin response latency up to 281.5 ± 41.5 s (P<0.001), in 96% neurons, that was partially restored by the CB2, but not the CB1 antagonist. Conclusion: 2-AG, 2-LG and 2-PG significantly delayed TRPV1 signalling in the majority of capsaicin-sensitive DRG neurons, that was markedly increased following combined application. Further studies of these endocannabinoids are required to identify the underlying mechanisms.
Endocannabinoids produced in photoreceptor cells in response to light activate Drosophila TRP channels
Sci Signal 2022 Oct 11;15(755):eabl6179.PMID:PMC9633101DOI:10.1126/scisignal.abl6179.
Drosophila phototransduction is a model for signaling cascades that culminate in the activation of transient receptor potential (TRP) cation channels. TRP and TRPL are the canonical TRP (TRPC) channels that are regulated by light stimulation of rhodopsin and engagement of Gαq and phospholipase Cβ (PLC). Lipid metabolite(s) generated downstream of PLC are essential for the activation of the TRPC channels in photoreceptor cells. We sought to identify the key lipids produced subsequent to PLC stimulation that contribute to channel activation. Here, using genetics, lipid analysis, and Ca2+ imaging, we found that light increased the amount of an abundant endocannabinoid, 2-Linoleoyl Glycerol (2-LG), in vivo. The increase in 2-LG amounts depended on the PLC and diacylglycerol lipase encoded by norpA and inaE, respectively. This endocannabinoid facilitated TRPC-dependent Ca2+ influx in a heterologous expression system and in dissociated ommatidia from compound eyes. Moreover, 2-LG and mechanical stimulation cooperatively activated TRPC channels in ommatidia. We propose that 2-LG is a physiologically relevant endocannabinoid that activates TRPC channels in photoreceptor cells.
Hyperthermia-Induced Seizures Enhance Brain Concentrations of the Endocannabinoid-Related Linoleoyl Glycerols in a Scn1a+/- Mouse Model of Dravet Syndrome
Cannabis Cannabinoid Res 2022 Oct 21.PMID:36269656DOI:10.1089/can.2022.0145.
Introduction: The endocannabinoid system contributes to the homeostatic response to seizure activity in epilepsy, a disease of brain hyperexcitability. Indeed, studies using conventional epilepsy models have shown that seizures increase endocannabinoids in the brain. However, it is unknown whether endocannabinoids and structurally related fatty acid amides and monoacylglycerols are similarly released in response to acute seizures in animal models of drug-resistant epilepsy. Therefore, in this study, we investigated whether a hyperthermia-induced seizure increased concentrations of endocannabinoids and related signaling lipids in the Scn1a+/- mouse model of Dravet syndrome. Materials and Methods: We compared hippocampal concentrations of the major endocannabinoids and related monoglycerols and N-acylethanolamines in wild-type mice, naïve Scn1a+/- mice, and Scn1a+/- mice primed with a single, hyperthermia-induced, generalized tonic-clonic seizure. Samples were collected 5 and 60 min following the seizure and then analyzed with LC-MS/MS. Results: We found that a hyperthermia-induced seizure in Scn1a+/- mice did not affect hippocampal concentrations of the major endocannabinoids, 2-AG and anandamide, or the N-acylethanolamines studied, although the sampling of tissue 5 min postseizure may have been too late to capture any effect on these lipids. Heterozygous deletion of Scn1a alone did not affect these lipid signaling molecules. Notably, however, we found that a hyperthermia-induced seizure significantly increased hippocampal concentrations of the monoacylglycerols, 2-Linoleoyl Glycerol (2-LG) and 1-linoleoyl glycerol (1-LG), in Scn1a+/- mice. Conclusions: Our results show the unprecedented elevation of the lesser-studied endocannabinoid-related monoacylglycerols, 2-LG and 1-LG, following a hyperthermia-induced seizure in a mouse model of Dravet syndrome. Future research is needed to comprehensively explore the function of these lipid signaling molecules during seizure activity and whether their actions can be exploited to develop new therapeutics.
Activation of TRPV1 by Capsaicin or Heat Drives Changes in 2-Acyl Glycerols and N-Acyl Ethanolamines in a Time, Dose, and Temperature Dependent Manner
Front Cell Dev Biol 2021 Apr 16;9:611952.PMID:33937226DOI:10.3389/fcell.2021.611952.
Endocannabinoids (eCBs) and transient receptor potential (TRP) channels are associated with thermoregulation; however, there are many gaps in the understanding of how these signaling systems work together in responding to changes in temperature. TRPV1, a calcium-permeable ion channel, is activated by capsaicin, elevated temperature, the eCB Anandamide, and over 15 additional endogenous lipids. There is also evidence for signaling crosstalk between TRPV1 and the eCB receptor, CB1. We recently found that activation of TRPV1-HEK cells by capsaicin increases the production of the eCB, 2-arachidonoyl glycerol (2-AG), suggesting a molecular link between these receptors. Here, we tested the hypothesis that TRPV1 activation by capsaicin drives regulation of a wider-range of lipid signaling molecules and is time and dose-dependent. We also tested the hypothesis that changes in temperature that drive changes in calcium mobilization in TRPV1-HEK will likewise drive similar changes in lipid signaling molecule regulation. Lipid analysis was conducted by partial purification of methanolic extracts on C18 solid phase extraction columns followed by HPLC/MS/MS. Capsaicin increased the release of 2-acyl glycerols (2-AG, 2-Linoleoyl Glycerol, 2-oleoyl glycerol), in a concentration- and time-dependent manner, whereas levels of N-acyl ethanolamines (NAEs), including Anandamide, were significantly decreased. Analogous changes in 2-acyl glycerols and NAEs were measured upon ramping the temperature from 37 to 45°C. In contrast, opposite effects were measured when analyzing lipids after they were maintained at 27°C and then quickly ramped to 37°C, wherein 2-acyl glycerol levels decreased and NAEs increased. These results provide further evidence that the eCB system and TRPV1 have integrated signaling functions that are associated with the molecular response to temperature variation.