Ceruletide (Caerulein) 是一种十肽和有效的胆囊收缩素受体激动剂。
Ceruletide, as a decapeptide and a potent cholecystokinetic agent, has a direct spasmogenic effect on the gallbladder muscle and bile ducts in humans and animals.[1]
In vitro experiment it indicated that at 1, 10, and 100 nmol/L, cerulein induced NF-kB–binding activity in a dose-dependent. But 0.3 nmol/L cerulein had no effect on activation NF-kappaB/Rel.[7]
In vivo, at a dose of 100 μg/kg, ceruletide decreased the rates of spontaneous locomotor activity and rearing, and also inhibited methylphenidate- and methamphetamine-induced hyperactivity in both sham-operated and vagotomized mice to same extent.[2] In vivo efficacy test it shown that rabbits were treated with 8 and 50 μg/kg of ceruletide decreased the plasma homovanillic acid levels, but had no significant differences. 140 and 200 μg/kg ceruletide had remarkable reduction of plasma homovanillic acid.[3] Ceruletide (100 μg/kg, s.c.) influenced the central dopaminergic system, enhanced the central effects of neuroleptics and had the potent therapeutic effects in the clinical trials.[4] In a mouse hypoxia model, treatment with 1-100 μg/kg ceruletide subcutaneously obviously prevented the CO-induced impairment of performance and the amelioration being correlated with the severity of hypoxia.[5] In addition, treatment with 10-300 μg/kg intraperitoneally ceruletide slightly but remarkably decreased the response rate (frequency of shuttles) under a discrete avoidance task in mice.[6]
参考文献:
[1].Vincent ME, et al. Pharmacology, clinical uses, and adverse effects of ceruletide, a cholecystokinetic agent. Pharmacotherapy. 1982 Jul-Aug;2(4):223-34.
[2].Moroji T, Hagino Y. Bilateral subdiaphragmatic vagotomy does not prevent the behavioral effects of systematically administered ceruletide in mice. Neuropeptides. 1987 Apr;9(3):217-24.
[3].Wakata N, et al. Effect of ceruletide on plasma monoamine metabolites in the rabbit. J Neurol Sci. 1991 May;103(1):97-100
[4].Hagino Y, Moroji T. Effect of ceruletide on discriminated avoidance behavior in rats. Neuropeptides. 1987 Nov-Dec;10(4):335-42.
[5].Maurice T, et al. Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice. J Pharmacol Exp Ther. 1994 May;269(2):665-73.
[6].Kuribara H, et al. Effects of ceruletide, administered singly and in combination with central-acting drugs, on discrete shuttle avoidance response in mice. Jpn J Pharmacol. 1990 Nov;54(3):325-9.
[7].Steinle AU, et al. NF-kappaB/Rel activation in cerulein pancreatitis. Gastroenterology. 1999 Feb;116(2):420-30.
Ceruletide 作为一种十肽和一种有效的胆囊收缩剂，对人类和动物的胆囊肌肉和胆管具有直接的痉挛作用。[1]
体外实验表明，在 1、10 和 100 nmol/L 时，雨蛙素以剂量依赖性方式诱导 NF-kB 结合活性。但0.3 nmol/L的雨蛙素对激活NF-kappaB/Rel没有影响。[7]
在体内，在 100 μg/kg 的剂量下，ceruletide 降低了假手术和迷走神经切断小鼠的自发运动活动和饲养率，并且还在相同程度上抑制了哌醋甲酯和甲基苯丙胺诱导的多动症。[2] 体内药效试验表明，兔用8和50μg/kg的ceruletide处理后血浆高香草酸水平降低，但无显着差异。 140和200 μg/kg ceruletide显着降低血浆高香草酸。[3] Ceruletide (100 μg/kg, s.c.)影响中枢多巴胺能系统，增强精神安定药的中枢作用，具有强效临床试验中的疗效。[4] 在小鼠缺氧模型中，皮下注射 1-100 μg/kg 的 ceruletide 可明显防止 CO 引起的性能损害，并且改善与严重程度相关[5]此外，用 10-300 μg/kg 腹腔注射 ceruletide 治疗小鼠在离散回避任务下的反应率（穿梭频率）略有但显着降低。[ 6]
| Cell experiment [1]: | |
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Cell lines |
Isolated rat pancreatic glands |
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Preparation Method |
An isolated external perfusion of a rat pancreas included a normal perfusion (KRB, 60 minutes), a long term perfusion (KRB, 240 minutes) and a perfusion (60 minutes) including an additive of the detergents triton x-100 or the cholecystokinin analogue ceruletide (1x10-8 M). |
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Reaction Conditions |
1x10-8 M; 60 or 240 min |
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Applications |
During a perfusion with the cholecystokinin analogue ceruletide (1x108 M), there is an increase of lipase after 30 minutes and an increase of amylase after 50 minutes perfusion. |
| Animal experiment [2]: | |
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Animal models |
Rats |
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Preparation Method |
Rats were i.v. infused for 6 h with either ceruletide (5 μg/kg/h) or ceruletide + Gabexate mesilate (50 mg/kg/h). |
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Dosage form |
5 μg/kg/h; i.v. |
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Applications |
In Gabexate mesilate-treated rats the serum amylase and trypsinogen concentrations were reduced by 60 and 80%, respectively, compared to rats infused with ceruletide alone. |
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参考文献: [1]. Mantke R, et al. Die isolierte extrakorporale Perfusion des Rattenpankreas - Ein Modell zur Untersuchung der Pathophysiologie der akuten Pankreatitis [The isolated perfused rat pancreas - an experimental model for investigation the early events in the pathogenesis of acute pancreatitis]. Zentralbl Chir. 2001 Nov;126(11):929-33. German. [2]. Wisner JR Jr, et al. Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat. Pancreas. 1987;2(2):181-6. |
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