JMV 449 是一种有效的神经降压素受体激动剂。
JMV 449 is a potent, long-lasting neurotensin receptor agonist[1,2]. JMV 499 inhibits the binding of 125I-neurotensin to newborn mouse brain homogenates (IC50=0.15nm), and contracts isolated guinea-pig ileum preparations(EC50=1.9nM)[3].
JMV 449 induced noticeable dose-dependent insulin releasing actions in BRIN-BD11 beta-cells. In combination with either GIP or GLP-1, JMV 449 augmented(P<0.05) the insulinotropic actions of both hormones, as well as enhancing (P<0.001) insulin secretory activity of both incretin peptides[4]. JMV 449 induced high affinity neurotensin receptor (NTR) gene activation in the human neuroblastoma cell line CHP212[5]. JMV 449 (1M) was found to increase tyrosine hydroxylase protein and mRNA abundance after short- and long-term treatments (5 or 72h) in CHP212 cell[6]
MV 449 (25nmol/kg) inhibited (P<0.05–P<0.001) food intake in overnight fasted lean mice, and enhanced (P<0.01) the appetite suppressing effects of an enzymatically stable GLP-1 mimetic. When injected co-jointly with glucose, JMV 449 evoked glucose lowering actions, but more interestingly significantly augmented (P<0.05) the glucose lowering effects of established long-acting GIP and GLP-1 receptor mimetics[4].JMV 449 induces hypothermia and is able to decrease the infarct size both 24h and 14 days after the onset of permanent focal ischaemia demonstrates its significant neuroprotective potential in mouse model of permanent focal ischaemia[7]
参考文献:
[1]. Dubuc I, Costentin J, et al. JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse. Eur J Pharmacol. 1992;219(2):327-329.
[2]. Craig SL, Gault VA, et al. Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control. Biochim Biophys Acta Gen Subj. 2021;1865(8):129917.
[3]. Lugrin D, Vecchini F, et al. Reduced peptide bond pseudopeptide analogues of neurotensin: binding and biological activities, and in vitro metabolic stability. Eur J Pharmacol. 1991;205(2):191-198.
[4]. Irwin N. Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control. Biochim Biophys Acta Gen Subj. 2021;1865(8):129917.
[5]. Najimi M, Souazé F, et al. Activation of receptor gene transcription is required to maintain cell sensitization after agonist exposure. Study on neurotensin receptor. J Biol Chem. 1998;273(34):21634-21641.
[6]. Najimi M, Hermans E, et al. Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP212 cells. Metab Brain Dis. 2001;16(3-4):165-174.
[7]. Torup L, Borsdal J, et al. Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia. Neurosci Lett. 2003;351(3):173-176.
JMV 449 是一种强效、长效的神经降压素受体激动剂[1,2]。 JMV 499 抑制125I-神经降压素与新生小鼠脑匀浆的结合（IC50=0.15nm），并收缩离体豚鼠回肠制剂（EC 50=1.9nM)[3].
JMV 449 在 BRIN-BD11 β 细胞中诱导显着的剂量依赖性胰岛素释放作用。结合 GIP 或 GLP-1，JMV 449 增强 (P<0.05) 两种激素的促胰岛素作用，以及增强 (P<0.001) 两种肠促胰岛素肽的胰岛素分泌活性[4]。 JMV 449 在人神经母细胞瘤细胞系 CHP212[5] 中诱导高亲和力神经降压素受体 (NTR) 基因激活。 JMV 449 (1M) 被发现在 CHP212 细胞中短期和长期处理（5 或 72 小时）后增加酪氨酸羟化酶蛋白和 mRNA 丰度[6]
MV 449 (25nmol/kg) 抑制 (P<0.05-P<0.001) 过夜禁食瘦小鼠的食物摄入，并增强 (P<0.01) 酶稳定 GLP-1 模拟物的食欲抑制作用。当与葡萄糖共同注射时，JMV 449 引起降糖作用，但更有趣的是显着增强 (P<0.05) 已建立的长效 GIP 和 GLP-1 受体模拟物的降糖作用[4].JMV 449 诱导低温并能够在永久性局灶性缺血发作后 24 小时和 14 天减少梗塞面积，证明其在永久性局灶性缺血小鼠模型中具有显着的神经保护潜力[7]
| Cell experiment [1]: | |
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Cell lines |
Rodent BRIN-BD11 beta-cells |
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Preparation Method |
Cells were incubated (20 min) with JMV 449 alone (1×10-4-1μM), or in combination with GIP (1×10-4-1μM) or GLP-1 (1×10-4-1μM), as well as combination of all three test peptides. |
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Reaction Conditions |
1×10-4-1μM JMV-449 |
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Applications |
JMV 449 displayed significant (P |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6 mice, 10 month old |
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Preparation Method |
Cumulative food intake was assessed in overnight fasted (18h) mice following i.p. injection of saline vehicle (0.9% w/v NaCl) or test peptide (JMV 449, (D-Ala2)GIP, and exendin-4), with food intake measured at 30min intervals for 180min. |
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Dosage form |
25nmol/kg |
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Applications |
JMV 449, (D-Ala2)GIP, and exendin-4, induced a significant (P2)GIP and JMV 449, together with 2.5nmol/kg exendin-4, there was a significant reduction (P2)GIP plus exendin-4 injection alone. |
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参考文献: [1]. Irwin N. Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control. Biochim Biophys Acta Gen Subj. 2021;1865(8):129917 |
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