CGRP 8-37 (human)
(Synonyms: 降钙素基因相关肽片段8-37人体,Human α-CGRP (8-37)) 目录号 : GC16147
CGRP 8-37 (human)是一种高选择性的CGRP受体拮抗剂。
Cas No.:119911-68-1
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
| Cell experiment [1]: | |
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Cell lines |
Rat VSMCs |
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Preparation Method |
Cells were pre-treated with or without test compounds for the indicated time periods and then stimulated with or without Ang II for 30 minutes and CGRP for 60 minutes. In some experiments, CGRP 8-37 (human) or H-89 was added 30 minutes, dibutyl-cAMP 60 minutes and apocynin 2 hours before CGRP treatment. |
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Reaction Conditions |
CGRP 8-37 (human) (3 × 10-5 mol/L) for 30 minute |
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Applications |
Pre-treatment with H-89 or CGRP 8-37 (human) also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague±Dawley rats (175±200 g) |
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Preparation Method |
Rts were given a spinal hemisection or a sham surgery at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. CGRP 8-37 (human) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. |
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Dosage form |
CGRP 8-37 (human)as1,5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volume. |
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Applications |
CGRP 8-37 (human) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. |
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References: [1]. Luo HM, Wu X, et,al. Calcitonin gene-related peptide inhibits angiotensin II-induced NADPH oxidase-dependent ROS via the Src/STAT3 signalling pathway. J Cell Mol Med. 2020 Jun;24(11):6426-6437. doi: 10.1111/jcmm.15288. Epub 2020 May 5. PMID: 32372557; PMCID: PMC7294141. | |
CGRP 8-37 (human)is a highly selective CGRP receptor antagonists.
CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II-induced VSMCs. The Ang II-stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre-treatment with H-89 or CGRP 8-37 (human) also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress[1].
CGRP 8-37 (human) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection[2].When explored the effects of calcitonin gene-related peptide (CGRP) and its antagonist CGRP 8-37 (human) on the latency to hindpaw withdrawal responses induced by both thermal and mechanical stimulation in rats. CGRP 8-37 (human) (5nM or 10nM) induced a significant increase in hindpay withdrawal latency[3,5].Intrathecal administration of CGRP 8-37 (human) can reversed the SP-induced decrease in latency to both withdrawal responses ,besides,it can mediated a significant increase in response latency [6].When performed to investigate the effects of intrathecal administration of CGRP 8-37 (human) on the HWL and HWT in rats with unilateral hindpaw inflammation induced by subcutaneous injection of carrageenin.Intrathecal administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation[4]. CGRP 8-37 (human) could enhance ALI induced by LPS in the rat model, and regulate the expression levels of AQP-1 and AQP-5 by affecting inflammatory cytokines[7]. CGRP8-37 and Endomorphin-1 alone, and in combinated administration, as bolus and continues dose.Endomorphin-1and CGRP 8-37 (human) injections were able to reduce neuropathic pain after spinal cord compression injury[8]. The presence of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was investigated. CGRP and its receptor antagonists, olcegepant and CGRP 8-37 (human), were microinjected into the vlPAG while changes of neural responses in the trigeminocervical complex (TCC) were monitored. Inhibition of TCC responses to stimulation of dural afferents and ophthalmic cutaneous receptive fields after microinjection of bicuculline into vlPAG indicated a connection between the vlPAG and TCC neurons. CGRP facilitated these TCC responses, whereas olcegepant and CGRP 8-37 (human) decreased them[9].
References:
[1]. Luo HM, Wu X, et,al. Calcitonin gene-related peptide inhibits angiotensin II-induced NADPH oxidase-dependent ROS via the Src/STAT3 signalling pathway. J Cell Mol Med. 2020 Jun;24(11):6426-6437. doi: 10.1111/jcmm.15288. Epub 2020 May 5. PMID: 32372557; PMCID: PMC7294141.
[2]. Bennett AD, Chastain KM, Hulsebosch CE. Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain. Pain. 2000 May;86(1-2):163-75. doi: 10.1016/s0304-3959(00)00242-6. PMID: 10779673.
[3]. Yu LC, Hansson P, et,al. The calcitonin gene-related peptide antagonist CGRP8-37 increases the latency to withdrawal responses in rats. Brain Res. 1994 Aug 8;653(1-2):223-30. doi: 10.1016/0006-8993(94)90393-x. Erratum in: Brain Res 1994 Dec 15;666(2):295. PMID: 7526959.
[4]. Yu LC, Hansson P, et,al. Intrathecal CGRP8-37-induced bilateral increase in hindpaw withdrawal latency in rats with unilateral inflammation. Br J Pharmacol. 1996 Jan;117(1):43-50. doi: 10.1111/j.1476-5381.1996.tb15152.x. PMID: 8825341; PMCID: PMC1909388.
[5]. L?fgren O, Yu LC, et,al. Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal latency in rats with a unilateral thermal injury. Neuropeptides. 1997 Dec;31(6):601-7. doi: 10.1016/s0143-4179(97)90006-8. PMID: 9574827.
[6]. Yu LC, Hansson P, et,al. Opioid antagonists naloxone, beta-funaltrexamine and naltrindole, but not nor-binaltorphimine, reverse the increased hindpaw withdrawal latency in rats induced by intrathecal administration of the calcitonin gene-related peptide antagonist CGRP8-37. Brain Res. 1995 Nov 6;698(1-2):23-9. doi: 10.1016/0006-8993(95)00752-c. PMID: 8581488.
[7]. Hong-Min F, Chun-Rong H, et,al.CGRP 8-37 enhances lipopolysaccharide-induced acute lung injury and regulating aquaporin 1 and 5 expressions in rats. J Physiol Biochem. 2016 Aug;73(3):381-386. doi: 10.1007/s13105-017-0563-3. Epub 2017 May 4. Erratum in: J Physiol Biochem. 2017 Oct 5;: PMID: 28470555.
[8]. Janzadeh A, Karami Z, et,al.The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats. J Chem Neuroanat. 2020 Jul;106:101771. doi: 10.1016/j.jchemneu.2020.101771. Epub 2020 Feb 21. PMID: 32092447.
[9].Pozo-Rosich P, Storer RJ, et,al. Periaqueductal gray calcitonin gene-related peptide modulates trigeminovascular neurons. Cephalalgia. 2015 Dec;35(14):1298-307. doi: 10.1177/0333102415576723. Epub 2015 Mar 19. PMID: 25792688.
CGRP 8-37 (human)是一种高选择性的CGRP受体拮抗剂。
CGRP 显着抑制 Ang II 诱导的 VSMC 中 NADPH 氧化酶产生的活性氧 (ROS) 水平。 Ang II 刺激的 Src 和下游转录因子 STAT3 的激活被 CGRP 消除。然而，随着组成型激活的 Src 或 STAT3 的表达，CGRP 的抗氧化作用丧失。用 H-89 或 CGRP 8-37（人）预处理也阻断了 CGRP 对 Ang II 诱导的氧化应激的抑制作用[1]。
CGRP 8-37（人）可有效消除脊髓半切产生的机械性和热性异常性疼痛[2]。当探索降钙素基因相关肽 (CGRP) 及其拮抗剂 CGRP 的作用时8-37（人类）关于大鼠热刺激和机械刺激引起的后爪退缩反应的潜伏期。 CGRP 8-37（人）（5nM 或 10nM）可显着增加 hindpay 退缩潜伏期[3,5]。CGRP 8-37（人）的鞘内给药可逆转 SP 诱导的减少在两种戒断反应的潜伏期中，此外，它可以介导反应潜伏期的显着增加[6]。在研究鞘内注射 CGRP 8-37（人）对 HWL 和皮下注射角叉菜胶诱导单侧后爪炎症大鼠的 HWT 鞘内注射 10 nmol CGRP8-37 可显着增加实验性炎症大鼠的 HWL 和 HWT[4]。 CGRP 8-37 (human)可增强大鼠LPS诱导的ALI，并通过影响炎性细胞因子调节AQP-1和AQP-5的表达水平[7]。 CGRP8-37 和 Endomorphin-1 单独给药，以及联合给药，作为推注和持续剂量。Endomorphin-1 和 CGRP 8-37（人）注射液能够减轻脊髓压迫损伤后的神经性疼痛[8]。研究了降钙素受体样受体 (CLR) 和受体活性修饰蛋白 1 (RAMP1) 的存在。将 CGRP 及其受体拮抗剂 olcegepant 和 CGRP 8-37（人）显微注射到 vlPAG 中，同时监测三叉神经颈复合体 (TCC) 中神经反应的变化。在将荷包牡丹碱显微注射到 vlPAG 后，TCC 对刺激硬脑膜传入神经和眼部皮肤感受野的反应的抑制表明 vlPAG 和 TCC 神经元之间存在联系。 CGRP 促进了这些 TCC 反应，而 olcegepant 和 CGRP 8-37（人类）降低了它们[9]。
| Cas No. | 119911-68-1 | SDF | |
| 别名 | 降钙素基因相关肽片段8-37人体,Human α-CGRP (8-37) | ||
| Canonical SMILES | CC(C[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)([H])C(C)C)([H])[C@@](O)([H])C)([H])CC1=CN=CN1)([H])CCCNC(N)=N)([H])CC(C)C)([H])C)([H])/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/C/C(O | ||
| 分子式 | C139H230N44O38 | 分子量 | 3125.59 |
| 溶解度 | Soluble to 0.50 mg/ml in sterile water | 储存条件 | Desiccate at -20°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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1 mg | 5 mg | 10 mg |
| 1 mM | 0.3199 mL | 1.5997 mL | 3.1994 mL |
| 5 mM | 0.064 mL | 0.3199 mL | 0.6399 mL |
| 10 mM | 0.032 mL | 0.16 mL | 0.3199 mL |
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Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)
From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.
BIBN4096BS and CGRP(8-37) antagonize the relaxant effects of alpha-CGRP more than those of beta-CGRP in human extracranial arteries
We hypothesize that dilatation of extracranial arteries during migraine could be caused by CGRP. We compared the relaxant effects of alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-calcitonin gene-related peptide (beta-CGRP) and the antagonism by BIBN4096BS and CGRP(8-37) on rings of human temporal and occipital arteries precontracted with KCl. beta-CGRP relaxed temporal (-logEC50M = 8.1) and occipital arteries (-logEC50M = 7.6) with 19-fold and 29-fold lower potencies respectively than alpha-CGRP. Nearly maximal effective concentrations of alpha-CGRP (4 nM) and beta-CGRP (50 nM) caused stable relaxations of the temporal artery for 4 h without fading. BIBN4094BS antagonized the effects of alpha-CGRP (pK(B) = 10.1 and 9.9, respectively) more than beta-CGRP (pK(B) = 9.3 and 9.2 respectively) on both temporal and occipital arteries. CGRP(8-37) antagonized the effects of alpha-CGRP (pK(B) = 6.6 and 6.4 respectively) more than beta-CGRP (pK(B) = 5.7 and 5.5 respectively) on both temporal and occipital arteries. Antagonism of the relaxant effects of alpha-CGRP (4 nM) and beta-CGRP (50 nM) by BIBN4096BS (10 and 100 nM) was reversible for beta-CGRP, but irreversible for alpha-CGRP, 1 h after BIBN4096BS washout. We conclude that alpha-CGRP and beta-CGRP interact either at different binding sites of the same CGRP receptor system or all together with different receptor systems in human extracranial arteries. BIBN4096BS binds more firmly to the receptor activated by alpha-CGRP than to the receptor activated by beta-CGRP.
Antagonism of calcitonin gene-related peptide (CGRP) by human CGRP-(8-37): role of CGRP in internal anal sphincter relaxation
We performed functional studies on the opossum internal anal sphincter (IAS) smooth muscle strips and receptor binding studies in the IAS smooth muscle membranes to examine the influence of: human calcitonin gene-related peptide (CGRP)-(8-37) on the fall in IAS tension caused by human CGRP I and CGRP II and on [125I]human CGRP I binding on the IAS smooth muscle membranes. We also compared the ability of [Tyr0]-rat CGRP 28-37 to displace the radioligand from the IAS membranes to that of human CGRP-(8-37). Human CGRP-(8-37) caused significant and dose-dependent right-ward shifts of the dose-response curves of both CGRP I and CGRP II on the IAS smooth muscle. The specific binding of [125I]human CGRP I to IAS smooth muscle membranes was time- and temperature-dependent. CGRP antagonists human CGRP-(8-37) and [Tyr0]-rat CGRP 28-37 and CGRP I and CGRP II caused dose-dependent displacement of the radioligand. Vasoactive intestinal polypeptide and calcitonin on the other hand had no significant effect on the radioligand binding. Tachyphylaxis and cross tachyphylaxis to the effects of CGRP I and CGRP II were observed. The CGRP antagonists and CGRP I and CGRP II tachyphylaxis failed to modify the fall in the IAS tension in response to neural stimulation by electrical field stimulation. From these studies we conclude: human CGRP-(8-37) and [Tyr0]-rat CGRP 28-37 may serve as potential antagonists of CGRP action; human CGRP I and CGRP II may act on the same receptor on the IAS smooth muscle; and CGRP may not play a significant role in the IAS relaxation in response to electrical field stimulation.
Antagonistic effect of human alpha-CGRP [8-37] on the in vivo regional haemodynamic actions of human alpha-CGRP
In conscious rats, infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) caused small, reversible reductions in hindquarters flow and vascular conductance only, whereas at a dose of 300 nmol/kg/min there was a tachycardia and an increase in mean arterial blood pressure, together with renal, mesenteric and hindquarters vasoconstrictions. Human alpha-CGRP (0.03 nmol/kg/min) caused tachycardia, hypotension, and transient renal, but sustained hindquarters, vasodilatation; these changes were accompanied by mesenteric vasoconstriction. Infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) during administration of human alpha-CGRP (0.03 nmol/kg/min) abolished the effects of the latter but these re-appeared when the human alpha-CGRP [8-37] infusion was stopped. This dose of human alpha-CGRP [8-37] did not affect cardiovascular responses to isoprenaline. These results indicate that human alpha-CGRP [8-37] is an effective antagonist of the cardiovascular actions of human alpha-CGRP in vivo.