Norepinephrine (Levarterenol; L-Noradrenaline) is a potent adrenergic receptor (AR) agonist. Norepinephrine activates α1, α2, β1 receptors.
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Norepinephrine Chemical Structure
CAS No. : 51-41-2
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Based on 29 publication(s) in Google Scholar
Other Forms of Norepinephrine:
Norepinephrine hydrochloride
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Norepinephrine bitartrate monohydrate
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Norepinephrine tartrate
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(Rac)-Norepinephrine-d3 formate
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Norepinephrine purchased from MedChemExpress. Usage Cited in:
Cardiovasc Res. 2018 Feb 1;114(2):300-311.
[Abstract]
Knockdown of GATA4 ameliorated morphology and functional changes in a Meox1 cell line with NE stimulation. Immunodetection of actin in HL-1 cells. Actin staining appeared green, and sections are counterstained blue with DAPI (40,6-diamidino-2-phenylindole).
Norepinephrine purchased from MedChemExpress. Usage Cited in:
J Nutr Biochem. 2018 May 1;58:110-118.
[Abstract]
PASMCs are pretreated with or not Norepinephrine (50 μM) or ICI 118,551 (5 nM), and α-SMA (D) are analyzed.
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Description
Norepinephrine (Levarterenol; L-Noradrenaline) is a potent adrenergic receptor (AR) agonist. Norepinephrine activates α1, α2, β1 receptors[1][2][3][4].
IC50 & Target[1][2]
α1-adrenergic receptor
α2-adrenergic receptor
Beta-1 adrenergic receptor
Microbial Metabolite
Human Endogenous Metabolite
In Vitro
Norepinephrine (NE) is generally considered to be a β1-subtype selective adrenergic agonist over β2-adrenoceptor. Norepinephrine(NE) also has direct activity at the β2-adrenoceptor in higher concentrations[1].
Adipocytes from the inguinal fat pad (iWA) or the interscapular fat pad (BA) are isolated from neonatal wild-type C57BL/6J mice and cultured. To examine the effect of activating AT2 upon β-adrenergic signaling, cAMP production is first assessed in response to Norepinephrine (NE, 10 μM) with or without CGP (10 nM) co-treatment.Norepinephrine (NE) increases cAMP as expected in iWA, and CGP does not alter this effectNorepinephrine (NE) is also known to induce lipolysis, and liberated fatty acids are required to functionally activate UCP1 protein and to stimulate heat production. CREB phosphorylation at Ser133 is increased after Norepinephrine (NE) treatment and significantly attenuated with CGP co-treatment in mouse iWA[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Norepinephrine Related Antibodies
In Vivo
Norepinephrine (NE) is generally considered to be a β1-subtype selective adrenergic agonist over β2-adrenoceptor. Norepinephrine(NE) also has direct activity at the β2-adrenoceptor in higher concentrations[1].
Adipocytes from the inguinal fat pad (iWA) or the interscapular fat pad (BA) are isolated from neonatal wild-type C57BL/6J mice and cultured. To examine the effect of activating AT2 upon β-adrenergic signaling, cAMP production is first assessed in response to Norepinephrine (NE, 10 μM) with or without CGP (10 nM) co-treatment.Norepinephrine (NE) increases cAMP as expected in iWA, and CGP does not alter this effectNorepinephrine (NE) is also known to induce lipolysis, and liberated fatty acids are required to functionally activate UCP1 protein and to stimulate heat production. CREB phosphorylation at Ser133 is increased after Norepinephrine (NE) treatment and significantly attenuated with CGP co-treatment in mouse iWA[3].
Induction of cardiomyopathy[5][6]
Background
Norepinephrine is a potent growth factor for cardiomyocytes, and long-term infusion of sub-hypertensive doses of Norepinephrine in animals can cause an increase in myocardial mass and left ventricular wall thickness. Norepinephrine activates the raf-1 kinase/MAP kinase cascade through α1 and β-adrenergic stimulation, and the signaling pathways from these two receptors work synergistically to induce cardiomyocyte hypertrophy.
Specific Mmodeling Methods
Rat: Spragues-Dawley rats • adult (6 months old) • Male &bull. Administration: Each rat was continuously injected with 100 μg/kg/h or 200 μg/kg/h through an osmotic minipump.
Note
Modeling Indicators
Molecular changes: Significantly increased Dnmt activity and the expressions of Dnmt1, 3a, and 3b in the left ventricle. Significantly increased the mRNA expressions of fetal genes ANP, BNP, and βMHC in the left ventricle. Significantly increased ROS production in the left ventricle and increased global genomic DNA methylation and gene-specific CpG methylation at the Egr-1 binding site of the left ventricular PKCε promoter region in a concentration-dependent manner. Increased lactate dehydrogenase release in a concentration-dependent manner.
Significantly reduced the left ventricular developed pressure and dP/dtmax, inducing the upregulation of myotrophin and downregulation of four-and-a-half LIM domains protein 2 (FHL2). Phenotype observations: Increased the myocardial infarction area and sustained the elevation of blood pressure. Induced cardiac hypertrophy and reduced cardiac contractility. Increased the left ventricular weight.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight
169.18
Formula
C8H11NO3
CAS No.
51-41-2
Appearance
Solid
Color
White to yellow
SMILES
OC1=CC=C([C@@H](O)CN)C=C1O
Structure Classification
Phenols
Polyphenols
Initial Source
Endogenous metabolite
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, protect from light, stored under nitrogen
*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (295.54 mM; ultrasonic and adjust pH to 2 with HCl; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : ≥ 1.69 mg/mL (9.99 mM)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
5.9109 mL
29.5543 mL
59.1086 mL
5 mM
1.1822 mL
5.9109 mL
11.8217 mL
10 mM
0.5911 mL
2.9554 mL
5.9109 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Brian P Ramos, et al. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007 Mar;113(3):523-36.
[Content Brief]
[2]. MacGregor DA, et al. Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes. Chest. 1996 Jan;109(1):194-200.
[Content Brief]
[3]. Littlejohn NK, et al. Suppression of Resting Metabolism by the Angiotensin AT2 Receptor. Cell Rep. 2016 Aug 9;16(6):1548-60.
[Content Brief]
[4]. Xinyu Xu, et al. Binding pathway determines norepinephrine selectivity for the human β 1 AR over β 2 AR. Cell Res. 2021 May;31(5):569-579.
[Content Brief]
[5]. Xiao D, et al. "Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats." Cardiovascular research 101.3 (2014): 373-382.
[Content Brief]
[6]. Yamazaki, et al. "Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both α1-and β-adrenoceptors." Circulation 95.5 (1997): 1260-1268.
Cell Assay
[2]
Subcutaneous preadipocytes derived from a 38-year old non-diabetic female donor are immortalized with TERT and HPV E6/E7. For the current studies, a stable diploid clone (referred to as clone B) with consistent differentiation capacity is isolated by ring cloning. Cells are grown in preadipocyte PGM2 media. Once cells are confluent, differentiation is induced by incubation in differentiation media consisting of dexamethasone, IBMX, indomethacin, and additional insulin. Cells are differentiated for 10 days. Prior to treatment, media is replaced with PGM2 media for one day and then switched to serum-free media overnight for treatments. Adipocytes are treated for 6 hours with vehicle, Norepinephrine (NE, 10 μM), CGP (10 nM), or Norepinephrine (NE) and CGP[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
[1]. Brian P Ramos, et al. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007 Mar;113(3):523-36.
[Content Brief]
[2]. MacGregor DA, et al. Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes. Chest. 1996 Jan;109(1):194-200.
[Content Brief]
[3]. Littlejohn NK, et al. Suppression of Resting Metabolism by the Angiotensin AT2 Receptor. Cell Rep. 2016 Aug 9;16(6):1548-60.
[Content Brief]
[4]. Xinyu Xu, et al. Binding pathway determines norepinephrine selectivity for the human β 1 AR over β 2 AR. Cell Res. 2021 May;31(5):569-579.
[Content Brief]
[5]. Xiao D, et al. "Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats." Cardiovascular research 101.3 (2014): 373-382.
[Content Brief]
[6]. Yamazaki, et al. "Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both α1-and β-adrenoceptors." Circulation 95.5 (1997): 1260-1268.
[1]. Brian P Ramos, et al. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007 Mar;113(3):523-36.
[2]. MacGregor DA, et al. Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes. Chest. 1996 Jan;109(1):194-200.
[3]. Littlejohn NK, et al. Suppression of Resting Metabolism by the Angiotensin AT2 Receptor. Cell Rep. 2016 Aug 9;16(6):1548-60.
[4]. Xinyu Xu, et al. Binding pathway determines norepinephrine selectivity for the human β 1 AR over β 2 AR. Cell Res. 2021 May;31(5):569-579.
[5]. Xiao D, et al. "Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats." Cardiovascular research 101.3 (2014): 373-382.
[6]. Yamazaki, et al. "Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both α1-and β-adrenoceptors." Circulation 95.5 (1997): 1260-1268.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
H2O / DMSO
1 mM
5.9109 mL
29.5543 mL
59.1086 mL
147.7716 mL
5 mM
1.1822 mL
5.9109 mL
11.8217 mL
29.5543 mL
DMSO
10 mM
0.5911 mL
2.9554 mL
5.9109 mL
14.7772 mL
15 mM
0.3941 mL
1.9703 mL
3.9406 mL
9.8514 mL
20 mM
0.2955 mL
1.4777 mL
2.9554 mL
7.3886 mL
25 mM
0.2364 mL
1.1822 mL
2.3643 mL
5.9109 mL
30 mM
0.1970 mL
0.9851 mL
1.9703 mL
4.9257 mL
40 mM
0.1478 mL
0.7389 mL
1.4777 mL
3.6943 mL
50 mM
0.1182 mL
0.5911 mL
1.1822 mL
2.9554 mL
60 mM
0.0985 mL
0.4926 mL
0.9851 mL
2.4629 mL
80 mM
0.0739 mL
0.3694 mL
0.7389 mL
1.8471 mL
100 mM
0.0591 mL
0.2955 mL
0.5911 mL
1.4777 mL
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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