Background
Sincalide(CCK-8) is a minor bioactive segment of CCK that retains most of the biological activities of CCK and is widely used to study CCK functions[1]. Sincalide is a rapid-acting, synthetic analog of cholecystokinin for intravenous use in postevacuation cholecystography, and has a variety of effects as a novel cardiovascular hormone[2,3].
Sincalide protects H9c2 cardiomyoblasts from Ang II-induced apoptosis partly via activation of the CCK1 receptor and the phosphatidyqinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway[1]. Sincalide can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite[4]. Sincalide dose-dependently inhibited METH-induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells[5]
Sincalide can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model[2]. Sincalide decreased RPE cells apoptosis partly induced by ONOO- in Sprague-Dawley rats and is a potential drug for therapy of diabetic retinopathy[6]. Intramuscular injection of sincalide (0.07μg/kg) induced remarkable contractions of the gallbladder in vivo, and the contraction was nearly abolished by premedication of atropine sulfate (0.015 mg/kg)[7]
参考文献:
[1]. Wang C, Yu H, et al. Protective effect of cholecystokinin octapeptide on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells. J Cell Biochem. 2020;121(7):3560-3569.
[2]. Wang C, Zhang C, et al. Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats. Int J Biochem Cell Biol. 2020;125:105793.
[3]. Maher KA. Kinevac (sincalide for injection)/Squibb Diagnostics. Gastroenterol Nurs. 1991;14(2):98-100.
[4]. Liu Y, Zhang Y, et al. Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells. Neural Regen Res. 2014;9(14):1402-1408.
[5]. Wen D, An M, et al. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway. Neurotoxicology. 2016;57:31-38.
[6]. Hao LN, Wang M, et al. Control of peroxyntrite-induced production of inducible nitric oxide synthase isoforms and antagonism of cholecystokinin octapeptide -8 in retinal pigment epithelial cells in vivo. Int J Ophthalmol. 2011;4(6):605-610.
[7]. Takahashi T, Yamamura T, et al. Effects of cholecystokinin-octapeptide on the human gallbladder both in vivo and in vitro. Gastroenterol Jpn. 1986;21(1):49-54.
辛卡利特(CCK-8)是CCK的一个次要生物活性片段，保留了CCK的大部分生物活性，被广泛用于研究CCK的功能[1]。辛卡利特是一种速效合成胆囊收缩素类似物，用于静脉内清空胆囊造影术，作为一种新型心血管激素具有多种作用[2,3]。
Sincalide 部分通过激活 CCK1 受体和磷脂酰肌醇-3 激酶/蛋白激酶 B (PI3K/Akt) 信号通路来保护 H9c2 心肌细胞免受 Ang II 诱导的细胞凋亡[1]。辛卡利特可以保护人视网膜色素上皮细胞免受过氧亚硝酸盐诱导的细胞凋亡[4]。辛卡利特通过激活 PC12 细胞和 CCK2 受体稳定转染的 HEK293 细胞中的 CCK2 受体亚型剂量依赖性地抑制 METH 诱导的细胞毒性作用[5]
辛卡利特可减轻心肌梗死大鼠模型的非梗死区纤维化，延缓左心室重构和心力衰竭进展[2]。 Sincalide 可降低 Sprague-Dawley 大鼠部分由 ONOO- 诱导的 RPE 细胞凋亡，是治疗糖尿病视网膜病变的潜在药物[6]。肌内注射辛卡利特（0.07μg/kg）可引起体内胆囊显着收缩，术前给予硫酸阿托品（0.015 mg/kg）后收缩几乎消失[7]
Protocol
| Cell experiment [1]: |
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Cell lines
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H9c2 cells
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Preparation Method
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H9c2 cells were incubated with sincalide (0.001, 0.01, 0.1, 1, 10, or 100μM) or Ang II (0.01, 0.1, 1, or 10μM) for 24 hours. Then treated the cells with sincalide at various concentrations (0.001, 0.01, 0.1, 1, 10, 100μM) before adding Ang II.
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Reaction Conditions
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0.001, 0.01, 0.1, 1, 10, or 100μM
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Applications
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Treatment with 1μM sincalide before exposure to 1μM Ang II significantly prevented cell death.
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| Animal experiment [2]: |
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Animal models
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Male Sprague-Dawley rats (200-220g, 6-7 weeks)
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Preparation Method
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Sincalide was dissolved in sterile normal saline to form a 50μg/mL stock solution. Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI+NaCl, and MI+sincalide. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with sincalide or saline for 28 days.
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Dosage form
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50μg/kg/d sincalide，intraperitoneal injection
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Applications
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Treatment with sincalide attenuated myocardial infarction-induced myocardial fibrosis, and delay the left ventricular remodeling and the progress of heart failure.
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参考文献:
[1]. Wang C, Yu H, et al. Protective effect of cholecystokinin octapeptide on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells. J Cell Biochem. 2020;121(7):3560-3569.
[2]. Wang C, Zhang C, et al. Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats. Int J Biochem Cell Biol. 2020;125:105793.
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