Astressin 2B
目录号 : GC15720
Astressin 2B 是促肾上腺皮质激素释放因子受体 2 (CRF2) 的选择性强效拮抗剂（IC50 值为 1.3 和 >；CRF2 和 CRF1 分别为 500 nM），可拮抗 CRF2 介导的胃排空抑制。
Cas No.:681260-70-8
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 |
A431 epidermoid cells |
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Preparation Method |
cells were pretreated overnight with Astressin 2b (1 µM). Non-adherent cells were removed by washing three times with PBS, and cell adhesion was estimated by a colorimetric cell proliferation assay. |
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Reaction Conditions |
Astressin 2b (1 µM) overnight |
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Applications |
Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats (240-280 g) |
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Preparation Method |
The animals were administered indomethacin and killed 24 h later under deep ether anesthesia. Ucn I (a CRFR1 and CRFR2 agonist: 2 20 µg/kg) or astressin (a nonselective CRFR antagonist: 50 µg/kg) was given i.v. 10 min before the administration of indomethacin. NBI-27914 or astressin 2B (60 µg/kg) was given i.v. 10 min before the administration of Ucn I or indomethacin. |
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Dosage form |
60 µg/kg astressin 2B |
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Applications |
Astressin 2B also exacerbated the intestinal ulcerogenic response induced by indomethacin. Urocortin I prevented indomethacin-induced intestinal lesions, together with the suppression of bacterial invasion and an increase in mucosal MPO activity and iNOS expression. Urocortin I suppressed the hypermotility response to indomethacin, and this effect was also abrogated by astressin-2B. |
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References: [1]. Pelissier-Rota M, Chartier NT,et,al. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells. Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1246-1259. doi: 10.1016/j.bbamcr.2017.04.008. Epub 2017 Apr 18. PMID: 28432022. | |
Astressin 2B is selective and potent antagonist of corticotropin-releasing factor receptor 2 (CRF2) (IC50 values are 1.3 and > 500 nM for CRF2 and CRF1 respectively) that antagonizes CRF2-mediated inhibition of gastric emptying.
Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling[4].
Astressin-2B also exacerbated the intestinal ulcerogenic response induced by indomethacin. Urocortin I prevented indomethacin-induced intestinal lesions, together with the suppression of bacterial invasion and an increase in mucosal MPO activity and iNOS expression. Urocortin I suppressed the hypermotility response to indomethacin, and this effect was also abrogated by astressin-2B[2]. In mcie, Central administration of Ucn1 increased significantly the number of entries into the chamber of the unknown male, without changing the time of interaction and this effect was blocked by astressin2B[1]. NmU, a potent endogenous anorectic, serves as a catabolic signaling molecule in the brain. For an investigation of the possible role of receptors in mediating hyperthermia, the animals were treated with astressin 2B, a CRH2 receptor antagonist. NmU increased the colon temperature, maximal action being observed at 2-3h[3].
References:
[1]. Bagosi Z, Karasz G, et,al. The effects of CRF and urocortins on the sociability of mice. Brain Res. 2017 May 15;1663:114-122. doi: 10.1016/j.brainres.2017.03.003. Epub 2017 Mar 14. PMID: 28315311.
[2]. Kubo Y, Kumano A, et,al. Urocortin prevents indomethacin-induced small intestinal lesions in rats through activation of CRF2 receptors. Dig Dis Sci. 2010 Jun;55(6):1570-80. doi: 10.1007/s10620-009-0930-1. Epub 2009 Aug 26. PMID: 19707872.
[3]. Telegdy G, Adamik A. Mediators involved in the hyperthermic action of neuromedin U in rats. Regul Pept. 2014 Jun-Aug;192-193:24-9. doi: 10.1016/j.regpep.2014.07.004. Epub 2014 Aug 7. PMID: 25108055.
[4]. Pelissier-Rota M, Chartier NT, et,al. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells. Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1246-1259. doi: 10.1016/j.bbamcr.2017.04.008. Epub 2017 Apr 18. PMID: 28432022.
Astressin 2B 是促肾上腺皮质激素释放因子受体 2 (CRF2) 的选择性强效拮抗剂（IC50 值为 1.3 和 >；CRF2 和 CRF1 分别为 500 nM），可拮抗 CRF2 介导的胃排空抑制。
Ach 介导的细胞粘附作用被 CRF2 拮抗剂 astressin 2b 阻断，表明 Ach 作用部分取决于 CRF2 信号[4]。
Astressin-2B 还加剧了吲哚美辛诱导的肠道溃疡反应。 Urocortin I 可预防吲哚美辛引起的肠道损伤，同时抑制细菌入侵并增加粘膜 MPO 活性和 iNOS 表达。 Urocortin I 抑制对吲哚美辛的过度运动反应，并且这种作用也被 astressin-2B[2] 消除。在 mcie 中，Ucn1 的中央管理显着增加了未知男性进入腔室的次数，而没有改变相互作用的时间，并且这种作用被 astressin2B[1] 阻断。 NmU 是一种有效的内源性厌食剂，在大脑中充当分解代谢信号分子。为了研究受体在介导体温过高中的可能作用，动物接受了 astressin 2B（一种 CRH2 受体拮抗剂）治疗。 NmU 增加结肠温度，在 2-3 小时观察到最大作用[3]。
| Cas No. | 681260-70-8 | SDF | |
| Canonical SMILES | CCCC[C@@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](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)([H])CC(O)=O)([H])CC(C)C)([H])CO)([H])CC1=CC=CC=C1)([H])CC2=CN=CN2)C)([H])CC(C)C)([H])CCCNC(N)=N)([H])CCCCN)( | ||
| 分子式 | C183H307N49O53 | 分子量 | 4041.69 |
| 溶解度 | Soluble to 1 mg/ml in Water | 储存条件 | Store 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 | 0.2474 mL | 1.2371 mL | 2.4742 mL |
| 5 mM | 0.0495 mL | 0.2474 mL | 0.4948 mL |
| 10 mM | 0.0247 mL | 0.1237 mL | 0.2474 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 | ||||||||||
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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.
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The effects of CRF and urocortins on the sociability of mice
Brain Res2017 May 15;1663:114-122.PMID: 28315311DOI: 10.1016/j.brainres.2017.03.003
The aim of our study was to determine the role of corticotropin-releasing factor (CRF), the urocortins (Ucn1, Ucn2 and Ucn3) and their receptors (CRF1 and CRF2) in the sociability of mice. Male CFLP mice were administered intracerebroventricularly (icv) with CRF and urocortins alone or in combination with antalarmin (specific CRF1 antagonist) and astressin2B (specific CRF2 antagonist) and then investigated in a Crawley social interaction test arena, that consists of three chambers. An unknown male in a cage was put in the first chamber and an empty cage was put in the opposite chamber. The tested male was habituated with the middle chamber for 5min and then allowed to explore the remaining chambers for 5min, during which the number of entries and the time of interaction were measured. Intracerebroventricular administration of CRF decreased significantly the number of entries and the time of interaction with the unknown male and these effects were blocked by antalarmin, but not astressin2B. In contrast, central administration of Ucn1 increased significantly the number of entries into the chamber of the unknown male, without changing the time of interaction and this effect was blocked by astressin2B, but not antalarmin. Central administration of Ucn2 and Ucn3 didn't influence remarkably the number of entries, but it reduced the time of interaction between the male mice. Our study suggests that CRF and Ucn1 may play important, but different roles in sociability, and that Ucn2 and Ucn3, playing similar roles, must be also involved in social interactions.
Involvement of CRH receptors in urocortin-induced hyperthermia
Peptides2008 Nov;29(11):1937-42.PMID: 18775757DOI: 10.1016/j.peptides.2008.07.028
The actions of individual corticotropin-releasing hormone (CRH) receptor (CRHR1 and CRHR2) were studied on the hyperthermia caused by urocortin 1, urocortin 2 and urocortin 3 in rats. Urocortin 1, urocortin 2 or urocortin 3 was injected into the lateral brain ventricle in conscious rats and the colon temperature was measured at different times following injection, up to 6h. In order to study the possible role of CRH receptors, the animals were treated with a urocortins together with the urocortin receptor inhibitors CRF 9-41, antalarmin and astressin 2B to influence the action of urocortins in initiating hyperthermia. Urocortin 1 at a dose of 2microg caused an increase in colon temperature, maximal action being observed in body temperature at 3h. CRH 9-41 and antalarmin, CRHR1 receptor antagonists, prevented the urocortin-induced increase in colon temperature while astressin 2B (CRHR2 receptor antagonist) was ineffective. Urocortin 2 at a dose of 2microg showed a byphasic action in increase in colon temperature having the first peak between 30 min and 1h and the second peak at 4h following treatment. CRF (9-41) and antalarmin was ineffective while astressin 2B fully blocked the action of urocortin 2. Urocortin 3 in a dose of lmicrog increased colon temperature; the maximal effect was observed at 2h. CRF (9-41) and antalarmin was ineffective while astressin 2B fully blocked the action of urocortin 3. The results demonstrated that urocortin 1, 2 or 3 when injected into the lateral brain ventricle caused increases in body temperature is mediated by urocortin receptors. The action of urocortin 1 is mediated by CRHR1 receptor, while in the action of urocortin 2 and urocortin 3 CRHR2 receptor is involved.
Involvement of CRF2 signaling in enterocyte differentiation
World J Gastroenterol2017 Jul 28;23(28):5127-5145.PMID: 28811708DOI: 10.3748/wjg.v23.i28.5127
Aim: To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation.
Methods: For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days). To assess the impact of CRF2 signaling on colonic cell differentiation, HT-29 and Caco-2 cells were exposed to Urocortin 3 recombinant proteins (Ucn3, 100 nmol/L). In some experiments, cells were pre-exposed to the astressin 2b (A2b) a CRF2 antagonist in order to inhibit the action of Ucn3. Intestinal cell differentiation was first analyzed by functional assays: the trans-cellular permeability and the para-cellular permeability were determined by Dextran-FITC intake and measure of the transepithelial electrical resistance respectively. Morphological modifications associated to epithelial dysfunction were analyzed by confocal microscopy after fluorescent labeling of actin (phaloidin-TRITC) and intercellular adhesion proteins such as E-cadherin, p120ctn, occludin and ZO-1. The establishment of mature adherens junctions (AJ) was monitored by following the distribution of AJ proteins in lipid raft fractions, after separation of cell lysates on sucrose gradients. Finally, the mRNA and the protein expression levels of characteristic markers of intestinal epithelial cell (IEC) differentiation such as the transcriptional factor kr¨¹ppel-like factor 4 (KLF4) or the dipeptidyl peptidase IV (DPPIV) were performed by RT-PCR and western blot respectively. The specific activities of DPPIV and alkaline phosphatase (AP) enzymes were determined by a colorimetric method.
Results: CRF2 protein is preferentially expressed in undifferentiated epithelial cells from the crypts of colon and in human colon carcinoma cell lines. Furthermore, CRF2 expression is down regulated according to the kinetic of HT-29 cell differentiation. By performing functional assays, we found that Ucn3-induced CRF2 signaling alters both para- and trans-cellular permeability of differentiated HT-29 and Caco-2 cells. These effects are partly mediated by Ucn3-induced morphological changes associated with the disruption of mature AJ in HT-29 cells and tight junctions (TJ) in Caco-2 cells. Ucn3-mediated activation of CRF2 decreases mRNA and protein expression levels of KLF4 a transcription factor involved in IEC differentiation. This signaling is correlated to a down-regulation of key IEC markers such as DPPIV and AP, at both transcriptional and post-transcriptional levels.
Conclusion: Our findings suggest that CRF2 signaling could modulate IEC differentiation. These mechanisms could be relevant to the stress induced epithelial alterations found in inflammatory bowel diseases.
Urocortin prevents indomethacin-induced small intestinal lesions in rats through activation of CRF2 receptors
Dig Dis Sci2010 Jun;55(6):1570-80.PMID: 19707872DOI: 10.1007/s10620-009-0930-1
Purpose: The role of corticotropin-releasing factor (CRF) in the pathogenesis of indomethacin-induced small intestinal lesions was examined in rats.
Methods: Animals were given indomethacin (10 mg/kg) subcutaneously and killed 24 h later. Urocortin I [a nonselective CRF receptor (CRFR) agonist], astressin (a nonselective CRFR antagonist), NBI-27914 (a CRFR1 antagonist), or astressin-2B (a CRFR2 antagonist) was given intravenously 10 min before the administration of indomethacin.
Results: Indomethacin caused hemorrhagic lesions in the small intestine, accompanied by intestinal hypermotility, mucosal invasion of enterobacteria, up-regulation of inducible nitric oxide synthase (iNOS) expression, and an increase of mucosal myeloperoxidase (MPO) activity. Pretreatment of the animals with astressin, a non-selective CRFR antagonist, aggravated the lesions in a dose-dependent manner. Likewise, astressin-2B also exacerbated the intestinal ulcerogenic response induced by indomethacin, while NBI-27914 did not. Urocortin I prevented indomethacin-induced intestinal lesions, together with the suppression of bacterial invasion and an increase in mucosal MPO activity and iNOS expression; these effects were significantly reversed by co-administration of astressin-2B but not NBI-27914. Urocortin I suppressed the hypermotility response to indomethacin, and this effect was also abrogated by astressin-2B but not NBI-27914.
Conclusions: These results suggest that urocortin 1 prevents indomethacin-induced small intestinal lesions, and that this action is mediated by the activation of CRFR2 and is functionally associated with the suppression of the intestinal hypermotility response caused by indomethacin. It is assumed that endogenous CRF contributes to the maintenance of the mucosal defensive ability of the small intestine against indomethacin through the activation of CRFR2.
Involvement of corticotropin-releasing factor and corticotropin-releasing factor 2 receptors in pathogenesis of ischemia/reperfusion-induced enteritis in rats
J Physiol Pharmacol2016 Oct;67(5):697-707.PMID: 28011950DOI: 10.3389/fphys.2021.660792
We herein investigated, using a corticotropin-releasing factor (CRF) agonist and antagonists, whether CRF plays a role in the pathogenesis of ischemia/reperfusion-induced small intestinal lesions in rats. Under pentobarbital anesthesia, the superior mesenteric artery was clamped (ischemia) for 75 min, followed by reperfusion with removal of the clamp. After a 24-h reperfusion, the area of hemorrhagic lesions that developed in the small intestine was measured. Urocortin I (CRF receptor 1/2 agonist), astressin (CRF receptor 1/2 antagonist), NBI27914 (CRF receptor 1 antagonist), or astressin 2B (CRF receptor 2 antagonist) was administered i.v. twice: 5 min before ischemia and 6 hours after reperfusion. Ischemia/reperfusion caused hemorrhagic lesions in the small intestine in ampicillin- and aminoguanidine-inhibitable manners, accompanied by enterobacterial invasion and the up-regulation of inducible nitric oxide synthase expression and myeloperoxidase activity. The severity of ischemia/reperfusion-induced lesions was significantly reduced by astressin and astressin 2B, but not by NBI27914, with the suppression of bacterial invasion, myeloperoxidase activity, and inducible nitric oxide synthase expression. In contrast, urocortin I markedly aggravated these lesions, and this response was completely abrogated by the co-administration of astressin 2B, but not NBI27914. The gene expression of CRF, CRF receptor 1, and CRF receptor 2 was observed in the small intestine, and remained unchanged following ischemia/reperfusion. These results suggest that ischemia/reperfusion caused hemorrhagic lesions in the small intestine, the pathogenesis of which involved enterobacteria and inducible nitric oxide synthase/nitric oxide. These lesions were aggravated by urocortin I in an astressin 2B-inhibitable manner, but suppressed by astressin in a CRF receptor 2-dependent manner. Endogenous CRF may be involved in the pathogenesis of ischemia/reperfusion-induced enteritis, possibly via the activation of peripheral CRF receptor 2.