(Leu¹⁵)-Gastrin I (human)
目录号 : GA20228
胃泌素是一种胃肠道激素，其结构类似于羧基末端氨基酸。
Cas No.:39024-57-2
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
| Kinase experiment [1]: | |
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Preparation Method |
Enzymic hydrolyses of gastrin analogues were analysed by HPLC Enzyme (0.005 unit) was incubated with substrate (0.1mM) and buffer in a final volume of 0.1mL. Buffer was 100mM-Tris/HCl, pH7.5, containing 0.3M-NaCl. When specific inhibitors of ACE were used, they were preincubated with the enzyme for 5-15min at 37℃. Reactions were carried out at 37℃ for various times and then stopped by freezing in liquid nitrogen. Samples (20μL) were stored at -80℃ before HPLC analysis. In kinetic studies, ACE (0.005 unit) was incubated with gastrin analogues at ten different substrate concentrations (ranging from 10 to 1000μM), in a buffer containing 300mM-NaCl. |
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Reaction Conditions |
10 to 1000μM |
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Applications |
The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. Hydrolysis of [Leu15]-gastrin-(14-17)-peptide in the presence of ACE was dependent on the chloride-ion concentration. Km values for the hydrolysis of [Leu15]-gastrin-(11-17)-peptide and [Leu15]-gastrin-(14-17)-peptide at an NaCl concentration of 300mm were respectively 420 and 3280μM, and the catalytic constants were about 115 and 885min-1. The kcat/Km for the reactions at 37℃ was approx. 0.28μM-1min-1. These results suggest that ACE might be involved in the metabolism in vivo of gastrin short fragments. |
| Animal experiment [2]: | |
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Animal models |
Sprague-Dawley rats, weighing 200±225g |
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Preparation Method |
Sprague-Dawley rats were given continuous subcutaneous infusion of human [Leu15]-gastrin-17 (5nmol/kg∙h) via osmotic minipumps, implanted in the neck under anaesthesia for 1, 2 or 6 days |
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Dosage form |
5nmol/kg∙h |
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Applications |
Hypergastrinaemia was induced by continuous infusion of human [Leu15]-gastrin-17 for 6 days. The treatment caused both vacuoles and lipofuscin bodies to appear in large numbers and the vacuoles disappeared promptly after interruption of the hypergastrinaemia, whereas the lipofuscin bodies remained. |
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References: [1]. Dubreuil P, Fulcrand P, et al. Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide. Biochem J. 1989;262(1):125-130. [2]. Zhao CM, Chen D, et al. ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation. Cell Tissue Res. 1998;291(2):315-323. |
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Gastrin is gastrointestinal hormones which is structurally similar in carboxy-terminal amino acids[1]. Gastrin are normally produced at high levels by endocrine (G) cells located in the gastric antrum and proximal duodenal mucosa. Gastrin can activate through the CCK2R several signaling pathways that have been linked to proliferation, cell adhesion, and antiapoptotic effects[2]. Human [Leu15]-gastrin-17 is a synthetic analogue of human gastrin-17 and is considered more stable than natural human [Met15]-gastrin-17 while having the same bioactivity[3]
[Leu15]-Gastrin Ⅰ can be synthesized use the Clt-resin[4]. Gastrin analogues can be hydrolyzed by angiotensin-converting enzyme(ACE), indicated that it is possible that administration of ACE inhibitors, used clinically as antihypertensive drugs, could affect the metabolism of gastrin fragments in vivo[5]
Human [Leu15]-gastrin Ⅰ directly modulated secretin binding to its receptors, that may involve in the inhibitory action of secretin on acid secretion induced by gastrin[1]. Continuous infusion of human [Leu15]-gastrin-17 via osmotic minipumps increased the plasma levels of gastrin. In the rats given the high dose(2.4nmol/kg∙h) of human [Leu15]-gastrin-17, the ECL-cell density, the mucosal histamine concentration and HDC activity increased significantly[3]. Continuous infusion of human [Leu15]-gastrin-17(5nmol/kg∙h) for 6 days induces hypergastrinaemia, and caused both vacuoles and lipofuscin bodies to appear in large numbers, suggesting that gastrin stimulates the development not only of vacuoles but also of lipofuscin, perhaps through enhanced autophagocytosis and/or oxidative stress[6]
References:
[1]. Iwakawa S, Nomura H, et al. Direct modulation of secretin binding sites by gastrin in the rat stomach. J Pharmacobiodyn. 1992;15(8):437-441.
[2]. Ferrand A, Wang TC. Gastrin and cancer: a review. Cancer Lett. 2006;238(1):15-29.
[3]. Ryberg B, Axelson J, et al. Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology. 1990;98(1):33-38.
[4]. Barlos K, Gatos D, et al. Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine. Int J Pept Protein Res. 1991;38(6):555-561.
[5]. Dubreuil P, Fulcrand P, et al. Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide. Biochem J. 1989;262(1):125-130.
[6]. Zhao CM, Chen D, et al. ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation. Cell Tissue Res. 1998;291(2):315-323.
胃泌素是一种胃肠道激素，其结构类似于羧基末端氨基酸[1]。胃泌素通常由位于胃窦和近端十二指肠粘膜的内分泌 (G) 细胞产生，含量较高。胃泌素可通过 CCK2R 激活数种与增殖、细胞粘附和抗细胞凋亡作用相关的信号通路[2]。人 [Leu15]-gastrin-17 是人 gastrin-17 的合成类似物，被认为比天然人 [Met15]-gastrin-17 更稳定，同时具有相同的生物活性[3]
[Leu15]-Gastrin Ⅰ可用Clt-resin[4]合成。胃泌素类似物可被血管紧张素转换酶(ACE)水解，表明临床上作为降压药使用的ACE抑制剂可能会影响胃泌素片段在体内的代谢[5]
人[Leu15]-胃泌素Ⅰ直接调节胰泌素与其受体的结合，可能参与了胰泌素对胃泌素诱导的胃酸分泌的抑制作用[1]。通过渗透性微型泵连续输注人 [Leu15]-胃泌素-17 会增加胃泌素的血浆水平。在给予高剂量（2.4nmol/kg?h）人[Leu15]-胃泌素-17的大鼠中，ECL-细胞密度、粘膜组胺浓度和HDC活性显着增加<sup >[3]。连续输注人[Leu15]-胃泌素-17(5nmol/kg?h)6天后出现高胃泌素血症，同时大量出现空泡和脂褐素体，提示胃泌素刺激可能通过增强的自噬作用和/或氧化应激，不仅产生液泡而且产生脂褐素[6]
| Cas No. | 39024-57-2 | SDF | |
| 分子式 | C98H126N20O31 | 分子量 | 2080.2 |
| 溶解度 | DMSO : 100 mg/mL (48.07 mM; Need ultrasonic); H2O : 10.53 mg/mL (5.06 mM; ultrasonic and adjust pH to 11 with NaOH) | 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 | 0.4807 mL | 2.4036 mL | 4.8072 mL |
| 5 mM | 0.0961 mL | 0.4807 mL | 0.9614 mL |
| 10 mM | 0.0481 mL | 0.2404 mL | 0.4807 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。
Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat
Gastroenterology1990 Jan;98(1):33-8.PMID: 2293597DOI: 10.1016/0016-5085(90)91287-g
This report describes the trophic effects of exogenous gastrin on the digestive tract and pancreas and the effect on the density of enterochromaffinlike cells in the oxyntic mucosa of the stomach. Female rats were given 1.2 or 2.4 nmol/kg.h of synthetic human [Leu15]-gastrin-17 for 28 days (via osmotic minipumps implanted subcutaneously). As a result, measurable plasma gastrin increased from about 230 pg/ml in the controls to about 500 and 800 pg/ml in the low- and high-dose groups, respectively. The trophic effects of gastrin were reflected in increased stomach weight and oxyntic mucosal mass. Gastrin also increased the enterochromaffinlike cell density and associated parameters (histamine concentration and histidine decarboxylase activity) but was without demonstrable effects on other parts of the digestive tract and pancreas. The results show that continuous infusion of exogenous gastrin for 28 days induces trophic changes similar to those seen after a period of hypergastrinemia induced by treatment with effective inhibitors of acid secretion.