Exendin-3 (9-39) amide
(Synonyms: 艾塞那肽,Avexitide;Exendin (9-39)) 目录号 : GC16482
Exendin3(9-39) amide 是一种特异性的 exendin 受体拮抗剂。
Cas No.:133514-43-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Raw264.7 macrophages |
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Preparation Method |
The cells were incubated with oxLDL (50 µg/mL), liraglutide (0.1, 0.5, 1 and 2 nmol/L) or exendin-3 (9-39) (1, 10 and 100 nM) alone, or in combination. |
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Reaction Conditions |
1, 10 and 100 nM, 37°C, 48h |
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Applications |
Compared with the liraglutide group, oxLDL-stimulated Raw264.7 cells-treated with excendin-3 (1-100 nmol/L) showed an increased ROS and MDA, but a decreased SOD in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Male Wistar rats |
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Preparation Method |
Group I: sham surgery rats. Rats were not subjected to nerve transection and the left sciatic nerve was gently exposed and muscle and skin are sutured. Group II: PSNT-vehicle group (nerve-transected group infused with saline). Group III: PSNT-TEN group (nerve-transected group infused with teneligliptin). Group IV: PSNT-TEN + EXE group (nerve-transected group infused with teneligliptin + Exendin-3 (9–39) amide). Group IV: PSNT-Mor (nerve-transected group infused with Morphine). The animal behavior test was performed on Day -1 (Pre-surgery), Day 7 (7 days post-surgery), and Day 8, day 10, Day 12, and Day 14. |
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Dosage form |
0.1 μg/1 μL/h, i.p. |
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Applications |
Co-infusion of 0.1 µg GLP-1 antagonist EXE did not reverse TEN-induced acute antinociception in PSNT rats. |
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References: [1]. Wang YG, et al. Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degeneration in Raw 264.7 cells involving the AMPK/SREBP1 pathway. J Geriatr Cardiol. 2015 Jul;12(4):410-6. [2]. Kuthati Y, et al. Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain. Antioxidants (Basel). 2021 Sep 9;10(9):1438. |
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Exendin3(9-39) amide is a specific exendin receptor antagonist. Exendin-3 increased cellular cAMP levels and amylase release from dispersed acini from guinea pig pancreas.[1]
In vitro experiment it shown that at 0.1-3 nM low concentrations caused a 12-fold increase in CAMP, whereas 0.3-3p~ higher concentrations caused an additional 24-fold increase in CAMP. Exendin-3 can interact with at least two receptors on guinea pig pancreatic acini; at >l00 nM high concentrations the peptide interacts with VIP receptors, so that a large increase in cAMP and stimulating amylase release; at 0.1-3 nM lower concentrations, the peptide interacts with a putative exendin receptor, result in causing a smaller increase in cAMP of undetermined function. And exendin-3(9-39) amide inhibits the actions of exendin-3 with IC 50 of 20 nM.[1] In oxLDL-stimulated Raw264.7 cells, treatment with 1-100 nmol/L excendin-3, it shown that an increased ROS and MDA, but a decreased SOD in a dose-dependent manner.[5] With 1 μM Exendin-3(9–39) pretreatment of the brain slice caused no change in the basal mPSC frequency, as well as no alteration in the basal firing rate was observed.[2]
In vivo experiment it demonstrated that Exendin-3 (9-39) amide (10x7 mol l-1) inhibits GLP-1R but no effect on GLP-2 induced inotropism, lusitropism and coronary motility.[3] In vivo experiment it shown that treatment with 100 nM exendin-3 (9-39) by luminally, the acceleratory effect of GLP-1 was blocked. [4]
References:
[1].Raufman JP, et al. Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9-39) amide, a specific exendin receptor antagonist. J Biol Chem. 1991 Feb 15;266(5):2897-902.
[2].Farkas I, et al. Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways. Front Cell Neurosci. 2016 Sep 12;10:214.
[3].Angelone T, et al. Receptor identification and physiological characterisation of glucagon-like peptide-2 in the rat heart. Nutr Metab Cardiovasc Dis. 2012 Jun;22(6):486-94.
[4].Nakamori H, et al. Mechanisms underlying the prokinetic effects of endogenous glucagon-like peptide-1 in the rat proximal colon. Am J Physiol Gastrointest Liver Physiol. 2021 Dec 1;321(6):G617-G627.
[5].Wang YG, et al. Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degeneration in Raw 264.7 cells involving the AMPK/SREBP1 pathway. J Geriatr Cardiol. 2015 Jul;12(4):410-6.
Exendin3(9-39) amide 是一种特异性的 exendin 受体拮抗剂。 Exendin-3 增加了豚鼠胰腺分散腺泡的细胞 cAMP 水平和淀粉酶释放。[1]
体外实验表明,在 0.1-3 nM 的低浓度下,CAMP 会增加 12 倍,而 0.3-3p~ 较高的浓度会导致 CAMP 增加 24 倍。 Exendin-3可与豚鼠胰腺腺泡上的至少两种受体相互作用；在 >l00 nM 高浓度下,该肽与 VIP 受体相互作用,使 cAMP 大量增加并刺激淀粉酶释放；在 0.1-3 nM 的较低浓度下,该肽与假定的毒蜥外泌肽受体相互作用,导致功能未定的 cAMP 的增加较小。 exendin-3(9-39) amide 抑制 exendin-3 的作用,IC 50 为 20 nM。[1] 在 oxLDL 刺激的 Raw264.7 细胞中,用 1-100 nmol/ L exendin-3, 它显示 ROS 和 MDA 增加,但 SOD 降低,呈剂量依赖性。[5] 用 1 μM Exendin-3(9-39) 预处理大脑切片不会引起基础 mPSC 频率的变化,也不会观察到基础放电率的变化。[2]
体内实验证明 Exendin-3 (9-39) 酰胺 (10x7 mol l-1) 抑制 GLP-1R,但对 GLP-2 诱导的收缩力、向心力和冠状动脉运动没有影响.[3]体内实验表明,100 nM exendin-3 (9-39) luminally 处理后,GLP-1 的加速作用被阻断。 [4]
| Cas No. | 133514-43-9 | SDF | |
| 别名 | 艾塞那肽,Avexitide;Exendin (9-39) | ||
| Canonical SMILES | CCC(C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(/N=C(O)/C(N)CC(O)=O)CC(C)C)CO)CCCCN)CCC(O)=N)CCSC)CCC(O)=O)CCC(O)=O)CCC(O)=O)C)C(C)C)CCCNC(N)=N)CC(C)C)CC1=CC=CC=C1)/C( | ||
| 分子式 | C149H234N40O47S | 分子量 | 3369.79 |
| 溶解度 | ≥ 168.5mg/mL in DMSO;Water100 mg/mL (29.68 mM);Ethanol100 mg/mL (29.68 mM) | 储存条件 | Desiccate at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.2968 mL | 1.4838 mL | 2.9675 mL |
| 5 mM | 0.0594 mL | 0.2968 mL | 0.5935 mL |
| 10 mM | 0.0297 mL | 0.1484 mL | 0.2968 mL |
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动物数量 | 只 |
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Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9-39) amide, a specific exendin receptor antagonist
Exendin-3 increased cellular cAMP levels and amylase release from dispersed acini from guinea pig pancreas. Low concentrations (0.1-3 nM) caused a 12-fold increase in cAMP, whereas higher concentrations (0.3-3 microM) caused an additional 24-fold increase in cAMP. Maximal cAMP with the highest concentration tested was the same as the maximal response with secretin, vasoactive intestinal peptide (VIP), peptide histidine isoleucine, helodermin, or helospectin-I. In terms of amylase release, exendin-3 had the same efficacy but was the least potent of these peptides. Exendin-3-induced increases in amylase release were inhibited by VIP receptor antagonists and the new peptide (greater than 0.1 microM) competed with radiolabeled VIP for binding sites on dispersed acini. Increasing concentrations of an exendin-3 fragment, exendin-3(9-39) amide, did not increase cAMP or amylase release but inhibited the increase in cAMP observed with 0.1-3 nM exendin-3. The fragment did not alter the effects of other peptides that are known to increase acinar cAMP. We conclude that exendin-3 interacts with at least two receptors on guinea pig pancreatic acini; at high concentrations (greater than 100 nM) the peptide interacts with VIP receptors, thereby causing a large increase in cAMP and stimulating amylase release; at lower concentrations (0.1-3 nM) the peptide interacts with a putative exendin receptor, thereby causing a smaller increase in cAMP of undetermined function. Exendin-3(9-39) amide is a specific exendin receptor antagonist.
Exendin peptides
Exendin-3 and exendin-4 are biologically active peptides isolated from venoms of the Gila monster lizards, H. horridum and H. suspectum, respectively. They were isolated using a chemical assay which detects peptides with amino-terminal histidine residues. Both are 39 amino acid peptides containing an amino-terminal histidine and a carboxyl-terminal serine amide and are members of the glucagon superfamily of peptide hormones. When tested in a dispersed pancreatic acinar cell assay, exendin-3 stimulates amylase release and with increasing concentrations causes a biphasic increase in cellular cAMP. In contrast, exendin-4 at concentrations up to 1 microM does not stimulate amylase release and produces a monophasic increase in cellular cAMP despite differing from exendin-3 by only two amino acid substitutions at positions 2 and 3 from the N-terminus. Endogenous Mammalian Analog to Exendins? The differences in biological activities can be explained by the observation that exendin-3 interacts with VIP receptors to stimulate amylase release, whereas exendin-4 does not. Both exendin-3 and exendin-4 interact with a putative exendin receptor on pancreatic acinar cells. The presence of this receptor was determined and defined by the ability of a specific inhibitor, exendin(9-39) amide, to abolish the increase in cAMP observed with 0.1-3 nM exendin-3 or exendin-4. The presence of the exendin receptor, although functionally undefined at the present time, predicts the existence of an endogenous mammalian analog to the exendin peptides.
Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas
The recent identification in Heloderma horridum venom of exendin-3, a new member of the glucagon superfamily that acts as a pancreatic secretagogue, prompted a search for a similar peptide in Heloderma suspectum venom. An amino acid sequencing assay for peptides containing an amino-terminal histidine residue (His1) was used to isolate a 39-amino acid peptide, exendin-4, from H. suspectum venom. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, but is otherwise identical. The structural differences make exendin-4 distinct from exendin-3 in its bioactivity. In dispersed acini from guinea pig pancreas, natural and synthetic exendin-4 stimulate a monophasic increase in cAMP beginning at 100 pM that plateaus at 10 nM. The exendin-4-induced increase in cAMP is inhibited progressively by increasing concentrations of the exendin receptor antagonist, exendin-(9-39) amide. Unlike exendin-3, exendin-4 does not stimulate a second rise in acinar cAMP at concentrations greater than 100 nM, does not stimulate amylase release, and does not inhibit the binding of radiolabeled vasoactive intestinal peptide to acini. This indicates that in dispersed pancreatic acini, exendin-4 interacts only with the recently described exendin receptor.
High potency antagonists of the pancreatic glucagon-like peptide-1 receptor
GLP-1-(7-36)-amide and exendin-4-(1-39) are glucagon-like peptide-1 (GLP-1) receptor agonists, whereas exendin-(9-39) is the only known antagonist. To analyze the transition from agonist to antagonist and to identify the amino acid residues involved in ligand activation of the GLP-1 receptor, we used exendin analogs with successive N-terminal truncations. Chinese hamster ovary cells stably transfected with the rat GLP-1 receptor were assayed for changes in intracellular cAMP caused by the test peptides in the absence or presence of half-maximal stimulatory doses of GLP-1. N-terminal truncation of a single amino acid reduced the agonist activity of the exendin peptide, whereas N-terminal truncation of 3-7 amino acids produced antagonists that were 4-10-fold more potent than exendin-(9-39). N-terminal truncation of GLP-1 by 2 amino acids resulted in weak agonist activity, but an 8-amino acid N-terminal truncation inactivated the peptide. Binding studies performed using 125I-labeled GLP-1 confirmed that all bioactive peptides specifically displaced tracer with high potency. In a set of exendin/GLP-1 chimeric peptides, substitution of GLP-1 sequences into exendin-(3-39) produced loss of antagonist activity with conversion to a weak agonist. The results show that receptor binding and activation occur in separate domains of exendin, but they are more closely coupled in GLP-1.
Glucagon-like peptide-1 receptors and sexual behaviors in male mice
The gut-brain peptide glucagon-like peptide-1 (GLP-1) reduces reward from palatable food and drugs of abuse. Recent rodent studies show that activation of GLP-1 receptors (GLP-1R) within the nucleus of the solitary tract (NTS) not only suppresses the motivation and intake of palatable food, but also reduces alcohol-related behaviors. As reward induced by addictive drugs and sexual behaviors involve similar neurocircuits, we hypothesized that activation of GLP-1R suppresses sexual behavior in sexually na?ve male mice. We initially identified that systemic administration of the GLP-1R agonist, exendin-4 (Ex4), decreased the frequency and duration of mounting behaviors, but did not alter the preference for females or female bedding. Thereafter infusion of Ex4 into the NTS decreased various behaviors of the sexual interaction chain, namely social, mounting and self-grooming behaviors. In male mice tested in the sexual interaction test, NTS-Ex4 increased dopamine turnover and enhanced serotonin levels in the nucleus accumbens (NAc). In addition, these mice displayed higher corticosterone, but not testosterone, levels in plasma. Finally, GLP-1R antagonist, exendin-3 (9-39) amide (Ex9), infused into the NTS differentially altered the ability of systemic-Ex4 to suppress the various behaviors of the sexual interaction chain, indicating that GLP-1R within the NTS is one of many sub-regions contributing to the GLP-1 dependent sexual behavior link. In these mice NTS-Ex9 partly blocked the systemic-Ex4 enhancement of corticosterone levels. Collectively, these data highlight that activation of GLP-1R, specifically those in the NTS, reduces sexual interaction behaviors in sexually na?ve male mice and further provide a link between NTS-GLP-1R activation and reward-related behaviors.