Caerulein (acetate)
(Synonyms: Ceruletide) 目录号 : GC43113
An oligopeptide
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Caerulein is an oligopeptide originally isolated from skin extracts of H. caerulea/L. caerulea. In vivo, caerulein increases the flow rate of gastric juices as well as pepsin and acid outputs in the gut of dogs, rats, and frogs. Caerulein (25-500 ng/kg) stimulates insulin secretion in a dose-dependent manner in anesthetized dogs. It is also used to induce pancreatitis in various animal models, as it increases autophagic vacuole formation and lysosomal enzyme activity leading to acinar cell necrosis when administered at a dose of 5 or 10 μg/kg per hour.
| Cas No. | SDF | ||
| 别名 | Ceruletide | ||
| Canonical SMILES | O=C([C@H](CC1=CNC2=C1C=CC=C2)NC(CNC([C@@]([H])(NC([C@H](CC3=CC=C(C=C3)OS(O)(=O)=O)NC([C@@H](NC([C@@H](NC([C@@H]4CCC(N4)=O)=O)CCC(N)=O)=O)CC(O)=O)=O)=O)[C@@H](C)O)=O)=O)N[C@H](C(N[C@H](C(N[C@@H](CC5=CC=CC=C5)C(N)=O)=O)CC(O)=O)=O)CCSC.CC(O)=O | ||
| 分子式 | C58H73N13O21S2•C2H4O2 | 分子量 | 1412.5 |
| 溶解度 | Water: 1 mg/ml | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.708 mL | 3.5398 mL | 7.0796 mL |
| 5 mM | 0.1416 mL | 0.708 mL | 1.4159 mL |
| 10 mM | 0.0708 mL | 0.354 mL | 0.708 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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。
Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration
Microbiome 2021 May 20;9(1):115.PMID:34016163DOI:10.1186/s40168-021-01065-2.
Background: The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis. Methods: Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of Caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota. Results: As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. Conclusions: The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.
Caerulein-induced NF-kappaB/Rel activation requires both Ca2+ and protein kinase C as messengers
Am J Physiol 1999 Sep;277(3):G678-86.PMID:10484394DOI:10.1152/ajpgi.1999.277.3.G678.
The eukaryotic transcription factor NF-kappaB/Rel is activated by a large variety of stimuli. We have recently shown that NF-kappaB/Rel is induced during the course of Caerulein pancreatitis. Here, we show that activation of NF-kappaB/Rel by Caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-kappaB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IkappaBalpha. IkappaBbeta was only slightly affected by Caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-kappaB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IkappaBalpha degradation and subsequent nuclear translocation of NF-kappaB/Rel induced by Caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-kappaB/Rel activation and IkappaBalpha degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-kappaB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-kappaB/Rel activation.
Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin
Am J Physiol Gastrointest Liver Physiol 2007 Jun;292(6):G1594-9.PMID:17332472DOI:10.1152/ajpgi.00500.2006.
Aberrant cytosolic Ca(2+) flux in pancreatic acinar cells is critical to the pathological pancreatic zymogen activation observed in acute pancreatitis, but the downstream effectors are not known. In this study, we examined the role of Ca(2+)-activated protein phosphatase 2B (or calcineurin) in zymogen activation. Isolated pancreatic acinar cells were stimulated with supraphysiological Caerulein (100 nM) with or without the calcineurin inhibitors FK506 or cell-permeable calcineurin inhibitory peptide (CiP). Chymotrypsin activity was measured as a marker of zymogen activation, and the percent amylase secretion was used as a measure of enzyme secretion. Cytosolic Ca(2+) changes were recorded in acinar cells loaded with the intermediate Ca(2+)-affinity dye fluo-5F using a scanning confocal microscope. A 50% reduction in chymotrypsin activity was observed after pretreatment with 1 microM FK506 or 10 microM CiP. These pretreatments did not affect amylase secretion or the rise in cytosolic Ca(2+) after Caerulein stimulation. These findings suggest that calcineurin mediates caerulein-induced intra-acinar zymogen activation but not enzyme secretion or the initial caerulein-induced cytosolic Ca(2+) signal.
Cholecystokinin JMV-180 and Caerulein effects on the pancreatic acinar cell cytoskeleton
Pancreas 1993 Sep;8(5):638-46.PMID:7508112DOI:10.1097/00006676-199309000-00018.
We previously demonstrated that the supramaximally effective concentrations of Caerulein caused marked changes in the apical cytoskeleton of the rat pancreatic acinar cell. These changes included ablation of microvilli, the terminal actin web, and intermediate filament bands. The present study was designed to elucidate part of the intracellular signalling mechanism mediating these changes. For these studies we used a cholecystokinin (CCK) analogue, CCK-JMV-180, that has been previously demonstrated not to inhibit enzyme secretion and to prevent the inhibition caused by Caerulein. We investigated the effects of CCK-JMV-180 alone and in combination with supramaximal concentrations of Caerulein on the morphology of the apical structures, on 1,2-diacylglycerol production (a measure of phospholipase C activity), and on amylase secretion in rat pancreatic acini. Supramaximally effective concentrations of Caerulein caused inhibition of enzyme secretion. CCK-JMV-180 had no effect on the ultrastructure of the apical region of the acinar cell and it prevented the ablation of apical cytoskeleton induced by a supramaximal concentration of Caerulein (10 nM). CCK-JMV-180 inhibited the increase in 1,2-diacylglycerol formation and the inhibition of amylase release caused by 10 nM Caerulein. Mimicking the effect of 1,2-diacylglycerol on activation of protein kinase C with phorbol 12-myristate 13-acetate and reproducing changes in [Ca2+]i caused by 10 nM Caerulein with 100 nM bombesin did not alter the apical cytoskeleton. These results suggest that the cytoskeletal changes observed with inhibitory concentrations of Caerulein are caused by the phospholipase C effects of Caerulein on membrane phospholipids.
Inhibition of Matrix Metalloproteinase with BB-94 Protects against Caerulein-Induced Pancreatitis via Modulating Neutrophil and Macrophage Activation
Gastroenterol Res Pract 2020 Apr 28;2020:8903610.PMID:32411205DOI:10.1155/2020/8903610.
Methods: AP was induced in Balb/C mice by ten hourly intraperitoneal injections of Caerulein (100 μg/kg) and LPS (5 mg/kg). The MMP inhibitor, BB-94 (20 mg/kg) was intraperitoneally administered 30 min before AP induction. Pancreatitis was confirmed by histology and serum amylase and lipase. Expression of pancreatic proinflammatory mediators and NF-κB activation were assessed. Bone marrow-derived neutrophils (BMDNs) and macrophages (BMDMs) were isolated. BMDNs were activated by phorbol 12-myristate 13-acetate (PMA, 50 ng/ml) and neutrophil reactive oxygen species (ROS) production was recorded. BMDMs were stimulated with 10 ng/ml IFN-γ and 100 ng/ml LPS to induce M1 macrophage polarization. Results: Pancreatic MMP-9 was markedly upregulated and serum MMP-9 was increased in caerulein-induced pancreatitis. Inhibition of MMP with BB-94 ameliorated pancreatic tissue damage and decreased the expression of proinflammatory cytokines (TNFα and IL-6) or chemokines (CCL2 and CXCL2) and NF-κB activation. Furthermore, using isolated BMDNs and BMDMs, we found that inhibition of MMP with BB-94 markedly decreased neutrophil ROS production, inhibited inflammatory macrophage polarization and NF-κB activation. Conclusions: Our results showed that inhibition of MMP with BB-94 protected against pancreatic inflammatory responses in caerulein-induced pancreatitis via modulating neutrophil and macrophage activation.