[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA是一种修饰的、具有选择性的神经肽Y Y1受体激动剂。
![[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA Chemical Structure](https://cdn.glpbio.com/thumbs/struct/GC7/GC72118.png "[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA Chemical Structure")
Sample solution is provided at 25 µL, 10mM.
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[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA is a modified, selective neuropeptide Y Y1 receptor agonist[1-2]. [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA activates the Y1 receptor to mimic the physiological effects of neuropeptide Y, while also modulating downstream signaling pathways to study related functions. [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA is used in research related to obesity, anxiety, and cardiovascular diseases[3-4].
In vitro, NGF-differentiated PC12 rat pheochromocytoma cells were treated with 1μM [Leu31,Pro34]-Neuropeptide Y TFA and 55mM KCl for 120 minutes. [Leu31,Pro34]-Neuropeptide Y TFA inhibited depolarization-stimulated DOPA (an intermediate in catecholamine synthesis) production[5]. 4T1 breast cancer cells were treated with [Leu31,Pro34]-Neuropeptide Y TFA (0.1-100nM) for 24 hours. [Leu31,Pro34]-Neuropeptide Y TFA did not promote endothelial cell tube formation (measured by branch points and complete network counts) and had no significant effect on vascular endothelial growth factor (VEGF) expression[6].
In vivo, [Leu31,Pro34]-Neuropeptide Y TFA (1.15-3.45nmol) was intracerebroventricularly administered to rats trained to discriminate neuropeptide Y (NPY) and to rats tested for feeding behavior. [Leu31,Pro34]-Neuropeptide Y TFA produced a discriminative stimulus effect similar to NPY and significantly increased food intake in the animals[7]. [Leu31,Pro34]-Neuropeptide Y TFA (2.3-23nmol in 10μl) was intrathecally administered to normal Sprague-Dawley rats and rats with unilateral sciatic nerve transection. [Leu31,Pro34]-Neuropeptide Y TFA elicited a biphasic effect on the flexor reflex (facilitation at low doses, and facilitation followed by inhibition at high doses) in both normal and nerve-transected rats[8].
References:
[1] Fuhlendorff J, Gether U, Aakerlund L, et al. [Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. Proc Natl Acad Sci U S A. 1990 Jan;87(1):182-6.
[2] Gobbi M, Mennini T, Vezzani A. Autoradiographic reevaluation of the binding properties of 125I-[Leu31,Pro34]peptide YY and 125I-peptide YY3-36 to neuropeptide Y receptor subtypes in rat forebrain. J Neurochem. 1999 Apr;72(4):1663-70.
[3] Gehlert DR, Gackenheimer SL, Schober DA. [Leu31-Pro34] neuropeptide Y identifies a subtype of 125I-labeled peptide YY binding sites in the rat brain. Neurochem Int. 1992 Jul;21(1):45-67.
[4] Hastings JA, Pavia JM, Morris MJ. Neuropeptide Y and [Leu31,Pro34]neuropeptide Y potentiate potassium-induced noradrenaline release in the paraventricular nucleus of the aged rat. Brain Res. 1997 Mar 7;750(1-2):301-4.
[5] McCullough LA, Westfall TC. Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells. Eur J Pharmacol. 1995 Dec 20;287(3):271-7.
[6] Medeiros PJ, Jackson DN. Neuropeptide Y Y5-receptor activation on breast cancer cells acts as a paracrine system that stimulates VEGF expression and secretion to promote angiogenesis. Peptides. 2013 Oct;48:106-13..
[7] Jewett DC, Cleary J, Schaal DW, et al. [Leu31,Pro34]neuropeptide Y (NPY), but not NPY 20-36, produces discriminative stimulus effects similar to NPY and induces food intake. Brain Res. 1993 Dec 17;631(1):129-32.
[8] Xu IS, Hao JX, Xu XJ, et al, The effect of intrathecal selective agonists of Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal and axotomized rats. Brain Res. 1999 Jul 3;833(2):251-7.
[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA是一种修饰的、具有选择性的神经肽Y Y1受体激动剂[1-2]。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA可激活Y1受体来模拟神经肽Y的生理效应，同时通过调节下游信号通路以研究相关功能。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA可用于肥胖、焦虑和心血管疾病的相关研究[3-4]。
在体外，[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA（1μM）处理与55mM KCl处理神经生长因子分化的PC12大鼠嗜铬细胞瘤细胞55分钟。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA能够抑制去极化刺激的DOPA（儿茶酚胺合成中间产物）的产生[5]。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA（0.1–100nM）处理4T1乳腺癌细胞24小时，对内皮细胞管状结构的形成（分支点数量和完整网络数量）没有产生促进作，对血管内皮生长因子（VEGF）的表达也无显著影响[6]。
在体内，[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA（1.15-3.45nmol）侧脑室注射于已训练辨别神经肽Y（NPY）的大鼠及测试摄食行为的大鼠。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA产生了与NPY类似的辨别刺激效应，并显著增加了动物的食物摄入量[7]。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA（2.3-23nmol；10μl）鞘内注射处理正常和单侧坐骨神经切断的Sprague-Dawley大鼠。[Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA在正常和神经切断大鼠中均引起屈曲反射的双相效应（低剂量促进，高剂量促进后抑制）[8]。
| Cell experiment [1]: | |
Cell lines | PC12 rat pheochromocytoma cells differentiated with nerve growth factor (NGF) |
Preparation Method | PC12 cells were grown and maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% fetal calf serum, 10% heat-inactivated horse serum, 2mM glutamine, 1mM pyruvate, 100U/ml penicillin, 100μg/ml streptomycin and 0.25μg/ml fungizone. For experiments, cells were plated and differentiated with NGF (50ng/ml) for 5 days. After differentiation, the medium was replaced with Krebs-Ringer Hepes buffer. The cells were incubated with [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA (1μM) in buffer supplemented with 55mM KCl and the decarboxylase inhibitor NSD-1015 (400μM) for 120 minutes. |
Reaction Conditions | 1μM; 55min. |
Applications | [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA significantly inhibited depolarization-stimulated 3,4-dihydroxyphenylalanine (DOPA) production, a measure of catecholamine synthesis. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats (intact sciatic nerve) and Sprague-Dawley rats with unilateral transection of the sciatic nerve (12-26 days prior to experiment) |
Preparation Method | Rats were decerebrated, spinalized, and artificially ventilated. A laminectomy was performed at mid-thoracic level for spinal cord transection. An intrathecal catheter was implanted with its tip on the lumbar spinal cord (L4-5). The flexor reflex was elicited by supramaximal electrical stimulation (0.5ms, 10mA, 1/min) of the sural nerve and recorded as electromyogram (EMG) activity from the ipsilateral hamstring muscles. After establishing a stable baseline reflex response, [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA (2.3-23nmol) was administered. |
Dosage form | 2.3-23nmol in 10μl; i.t.; acute single injection. |
Applications | [Leu31,Pro34]-Neuropeptide Y(human,rat,mouse) TFA produced a biphasic effect on the flexor reflex. Low doses facilitated the reflex. High doses (2.3 and 23nmol) induced an initial facilitation followed by a significant, dose-dependent, and reversible depression lasting 30-90 minutes. The magnitude and duration of the facilitatory and depressive effects were similar in both intact and sciatic nerve-injured rats. |
References: | |
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