Substance P 1-7
目录号 : GC37696
Substance P (7-11) 是神经肽P物质 (SP) 的片段。Substance P (7-11) 可对孤束核产生抑制和缓和作用。
Cas No.:68060-49-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats[1]Sprague-Dawley male rats weighing 250-300 g are anaesthetized with halothane and placed in a stereotaxic frame. An injection cannula, conically shaped with a penetration tip diameter of approximately 0.15 mm is loared into the SNR. Saline (0.2 μL), SP (0.007-0.7 nM) or Substance P (7-11) (0.01-1 nM) is injected into the left substantia nigra, pars reticulata (SNR) and the rat is placed in a rotometer. The substances are injected in a total volume of 0.2 μL over a period of 1 min. A group of animals is sacrificed by decapitation 1 hour after the injection, their brains are immediately removed and tissue samples are taken from left and right striatum, globus pallidum (GP) and substantia nigra (SN). Samples are assayed for SP and SP(1-7)[1].Mice[2] The accumulated response time (s) of reciprocal movements of hindlimb scratching, biting, fore- and hindpaw licking are measured in Male mice (STD strain, 23-28 g) during the whole period of aversive response and 20 min at maximum. Substance P (7-11) is tested for its ability to inhibit the aversive response produced by intrathecal injection of SP or SP(5-11) (0.1 nM/mouse). Substance P (7-11) (1, 2, 4 pM) is then administered together with SP or SP(5-11)[2]. |
References: [1]. Herrera-Marschitz M, et al. The substance P(1-7) fragment is a potent modulator of substance P actions in the brain. Brain Res. 1990 Jun 25;521(1-2):316-20. | |
Substance P (7-11) is a fragment of the neuropeptide, substance P (SP). Substance P (7-11) gives depressor and bradycardic effects when applied to the nucleus tractus solitarius.
Substance P (7-11) is found to act as a very potent antagonist against the SP-induced responses and is formed locally in the nigra after SP injection. It is proposed that Substance P (7-11) is an endogenous modulator of SP actions[1]. Injection of low doses of Substance P (7-11) (1.0-4.0 pM simultaneously with SP or SP(5-11) (0.1 nM), reduce aversive behaviours induced by SP or SP(5- 11) significantly. These results indicate that SP(1-7) formed endogenously could modulate the actions of SP or SP(5-11) in the spinal cord[2].
[1]. Herrera-Marschitz M, et al. The substance P(1-7) fragment is a potent modulator of substance P actions in the brain. Brain Res. 1990 Jun 25;521(1-2):316-20. [2]. Sakurada T, et al. Substance P(1-7) antagonizes substance P-induced aversive behaviour in mice. Neurosci Lett. 1988 Dec 19;95(1-3):281-5.
| Cas No. | 68060-49-1 | SDF | |
| 分子式 | C41H65N13O10 | 分子量 | 900.04 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1111 mL | 5.5553 mL | 11.1106 mL |
| 5 mM | 0.2222 mL | 1.1111 mL | 2.2221 mL |
| 10 mM | 0.1111 mL | 0.5555 mL | 1.1111 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 |
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| % 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。
Impact of N-methylation of the Substance P 1-7 amide on anti-allodynic effect in mice after peripheral administration
Eur J Pharm Sci 2017 Nov 15;109:533-540.PMID:28887235DOI:10.1016/j.ejps.2017.09.007.
Substance P 1-7 (SP1-7, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic degradation of the tachykinin substance P (SP). This heptapeptide often opposes the effects of the mother peptide. Hence, SP1-7 is having anti-inflammatory, anti-nociceptive and anti-hyperalgesic effects in experimental models. Despite all encouraging properties of SP1-7 its exact mode of action has not yet been elucidated which has hampered further development of this heptapeptide in drug discovery. Contrary to SP that mediates its biological activity via the NK-1 receptor, the N-terminal fragment SP1-7 acts through an unknown target that is distinct from all known opioid and tachykinin receptors. The SP1-7 amide 1 (Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) was previously shown to be superior to the endogenous SP1-7 in all experimental pain models where the two compounds were compared. Herein, we report that N-methylation scan of the backbone of the SP1-7 amide (1) results in peptides that are significantly less prone to undergo proteolysis in plasma from both mouse and human. However, with the two exceptions of the [MeLys3]SP1-7 amide (3) and the [MeGln5]SP1-7 amide (4), the peptides with a methyl group attached to the backbone are devoid of significant anti-allodynic effects after peripheral administration in the spared nerve injury (SNI) mouse model of neuropathic pain. It is suggested that the N-methylation does not allow these peptides to form the accurate bioactive conformations or interactions required for efficient binding to the macromolecular target. The importance of intact N-terminal Arg1 and C-terminal Phe7, anticipated to serve as address and message residues, respectively, for achieving the anti-allodynic effect is emphasized. Notably, the three heptapeptides: the SP1-7 amide (1), the [MeLys3]SP1-7 amide (3) amide and the [MeGln5]SP1-7 amide (4) are all considerably more effective in the SNI mouse model than gabapentin that is widely used in the clinic for treatment of neuropathic pain.
Importance of N- and C-terminal residues of Substance P 1-7 for alleviating allodynia in mice after peripheral administration
Eur J Pharm Sci 2017 Aug 30;106:345-351.PMID:28587787DOI:10.1016/j.ejps.2017.06.004.
The heptapeptide SP1-7 (1, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic processing of the neuropeptide substance P (SP, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-Phe8-Gly9-Leu10-Met11-NH2). The heptapeptide 1 frequently exhibits opposite effects to those induced by SP, such as exerting antinociception, or attenuating thermal hyperalgesia and mechanical allodynia. The heptapeptide SP1-7 amide (2, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) is often more efficacious than 1 in experimental pain models. We have now assessed the anti-allodynic outcome after systemic administration of 2 and a series of Ala-substituted and truncated analogues of 2, in the spared nerve injury (SNI) mice model and the results obtained were correlated with in vitro plasma stability and permeability measurements. It is herein demonstrated that an intact Arg1 in SP1-7 amide analogues is fundamental for retaining a potent in vivo effect, while Lys3 of 2 is less important. A displacement with Ala1 or truncation rendered the peptide analogues either inactive or with a significantly attenuated in vivo activity. Thus, the pentapeptide SP3-7 amide (7, t1/2=11.1 min) proven to be the major metabolite of 2, demonstrated an in vivo effect itself although considerably less significant than 2 in the SNI model. Intraperitoneal administration of 2 in a low dose furnished the most powerful anti-allodynic effect in the SNI model of all the analogous evaluated, despite a fast proteolysis of 2 in plasma (t1/2=6.4 min). It is concluded that not only the C-terminal residue, that we previously demonstrated, but also the N-terminal with its basic side chain, are important for achieving effective pain relief. This information is of value for the further design process aimed at identifying more drug-like SP1-7 amide related peptidomimetics with pronounced anti-allodynic effects.
N-terminal truncations of Substance P 1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
Eur J Pharmacol 2014 Sep 5;738:319-25.PMID:24933646DOI:10.1016/j.ejphar.2014.05.060.
Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the biodistribution and stability of the peptides. Most of the examined compounds alleviated mechanical allodynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by any of the compounds tested. Most of the amino acids in the heptapeptide structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapeptide and its N-terminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel Substance P 1-7 analogues
ACS Med Chem Lett 2014 Oct 29;5(12):1272-7.PMID:25516784DOI:10.1021/ml5002954.
The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.