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Urocortin II, human Sale

目录号 : GC37868

A neuropeptide hormone

Urocortin II, human Chemical Structure

Cas No.:351999-18-3

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产品描述

Urocortin II is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF, urocortin , urocortin III , frog sauvagine, and piscine urotensin I.1 Human urocortin II shares 34, 43, and 37-40% sequence homology with rat and human CRF, human urocortin , and human urocortin III . Urocortin II increases cell shortening and accelerates relaxation of rabbit ventricular myocytes in a time- and concentration-dependent manner. In vivo, urocortin reduces arterial blood pressure in normotensive and spontaneously hypertensive rats via peripheral CRF2 receptor agonism. It induces dose-dependent tachycardia and hypotension in rats when administered at doses of 3 and 30 pmol/kg.2 Urocortin (10 and 20 μg/kg) also reduces the visceral pain response to colorectal distension in conscious rats and delays gastric emptying in mice.1,3

1.Ad?o, R., Santos-Ribeiro, D., Rademaker, M.T., et al.Urocortin 2 in cardiovascular health and diseaseDrug Discov. Today20(7)906-914(2015) 2.Gardiner, S.M., March, J.E., Kemp, P.A., et al.Regional hemodynamic actions of selective corticotropin-releasing factor type 2 receptor ligands in conscious ratsJ. Pharmacol. Exp. Ther.312(1)53-60(2005) 3.Million, M., Wang, L., Wang, Y., et al.CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in ratsGut55(2)172-181(2006)

Chemical Properties

Cas No. 351999-18-3 SDF
分子式 C194H339N63O54S 分子量 4450.28
溶解度 Soluble in DMSO 储存条件 Store at -20°C
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1 mM 0.2247 mL 1.1235 mL 2.247 mL
5 mM 0.0449 mL 0.2247 mL 0.4494 mL
10 mM 0.0225 mL 0.1124 mL 0.2247 mL
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Research Update

Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2alpha

Gut 2007 Sep;56(9):1210-7.PMID:17412781DOI:10.1136/gut.2006.110668.

Background/aims: Urocortin II (UcnII) is a neuropeptide that binds with high affinity to the corticotropin-releasing hormone receptor 2 (CRHR2) in peripheral tissues. UcnII is synthesised in the intestine, but its role in human intestinal inflammation is largely unknown. Methods: Responses of human colonic epithelial cells expressing CRHR2 to stimulation by UcnII were measured using ELISA, western blot analysis, real-time reverse transcription-PCR (RT-PCR) and interleukin (IL)8 promoter activity. Expression levels of CRHR2 and UcnII in human colitis were determined by immunofluorescence and real-time RT-PCR in mucosal biopsies from patients with Crohn's and ulcerative colitis, and in human intestinal xenografts after exposure to Clostridium difficile toxin A. Results: It is reported here that expression of CRHR2 mRNA and protein in human colonic epithelial cells (HT-29) are increased by exposure to C difficile toxin A or tumour necrosis factor (TNF)alpha. Stimulation of non-transformed NCM460 colonocytes overexpressing CRHR2alpha receptor with UcnII resulted in a time- and concentration-dependent increase in IL8 production. UcnII stimulation also led to activation of nuclear factor-kappaB (NF-kappaB) and mitogen-acivated protein (MAP) kinase in these cells, as evidenced by degradation of IkappaBalpha and phosphorylation of the p65 subunit of NF-kappaB and extracellularly regulated kinase (ERK) 1/2. Furthermore, expression of UcnII and CRHR2 mRNA was increased in mucosal samples of patients with inflammatory bowel disease, and after exposure of human intestinal xenografts to C difficile toxin A. Conclusions: These results suggest that UcnII has pro-inflammatory effects in human intestinal cells via the CRHR2alpha receptor and may play an important role in the pathophysiology of colitis in humans.

Protective role of the neuropeptide Urocortin II against experimental sepsis and leishmaniasis by direct killing of pathogens

J Immunol 2013 Dec 15;191(12):6040-51.PMID:24249730DOI:10.4049/jimmunol.1301921.

We currently face an alarming resurgence in infectious diseases characterized by antimicrobial resistance and therapeutic failure. This has generated the urgent need of developing new therapeutic approaches that include agents with nontraditional modes of action. A recent interest focused on approaches based on our natural immune defenses, especially on peptides that combine innate antimicrobial activity against diverse pathogens and immunoregulatory functions. In this study, to our knowledge, we describe for the first time the antimicrobial activity of the neuropeptide Urocortin II (UCNII) against a panel of Gram-positive and Gram-negative bacteria and tropical parasites of the genus Leishmania. Importantly, this cytotoxicity was selective for pathogens, because UCNII did not affect mammalian cell viability. Structurally, UCNII has a cationic and amphipathic design that resembles antimicrobial peptides. Using mutants and UCNII fragments, we determined the structural requirements for the interaction between the peptide and the surface of pathogen. Following its binding to pathogen, UCNII caused cell death through different membrane-disrupting mechanisms that involve aggregation and membrane depolarization in bacteria and pore formation in Leishmania. Noteworthily, UCNII killed the infective form of Leishmania major even inside the infected macrophages. Consequently, UCNII prevented mortality caused by polymicrobial sepsis and ameliorated pathological signs of cutaneous leishmaniasis. Besides its presence in body physical and mucosal barriers, we found that innate immune cells produce UCNII in response to infections. Therefore, UCNII could be considered as an ancient highly-conserved host peptide involved in the natural antimicrobial defense and emerge as an attractive alternative to current treatments for microbial disorders with associated drug resistances.

TAS1R3 and UCN2 Transcript Levels in Blood Cells Are Associated With Sugary and Fatty Food Consumption in Children

J Clin Endocrinol Metab 2015 Sep;100(9):3556-64.PMID:26168276DOI:10.1210/JC.2015-1976.

Context: New types of dietary exposure biomarkers are needed to implement effective strategies for obesity prevention in children. Of special interest are biomarkers of consumption of food rich in simple sugars and fat because their intake has been associated with obesity development. Peripheral blood cells (PBCs) represent a promising new tool for identifying novel, transcript-based biomarkers. Objective: This study aimed to study potential associations between the transcripts of taste receptor type 1 member 3 (TAS1R3) and Urocortin II (UCN2) genes in PBCs and the frequency of sugary and fatty food consumption in children. Design, setting, and participants: Four hundred sixty-three children from the IDEFICS cohort were selected to include a similar number of boys and girls, both normal-weight and overweight, belonging to eight European countries. Main outcome measures: Anthropometric parameters (measured at baseline and in a subset of 193 children after 2 years), food consumption frequency and transcript levels of TAS1R3 and UCN2 genes in PBCs were measured. Results: Children with low-frequency consumption of sugary foods displayed higher TAS1R3 expression levels with respect to those with intermediate or high frequency. In turn, children with high-frequency consumption of fatty foods showed lower UCN2 expression levels with respect to those with low or intermediate frequency. Moreover, transcripts of TAS1R3 were related with body mass index and fat-mass changes after a 2-year follow-up period, with low expression levels of this gene being related with increased fat accumulation over time. Conclusion: The transcripts of TAS1R3 and UCN2 in PBCs may be considered potential biomarkers of consumption of sugary and fatty food, respectively, to complement data of food-intake questionnaires.