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| Targets |
Neurokinin A(4-10) targets the tachykinin NK₂ receptor (NK₂R), a G protein-coupled receptor that is activated by neurokinin A. The full-length Neurokinin A and its truncated form NKA(4-10) are potent spasmogens of human colon circular muscle, with this action mediated exclusively via tachykinin NK₂ receptors. The NK₂ receptor is widely distributed in the central nervous system, peripheral tissues, and smooth muscle, where it mediates various physiological functions including smooth muscle contraction, pain transmission, and inflammatory responses. The peptide shows high selectivity for NK₂ receptors over NK₁ and NK₃ receptors, making it a valuable tool for studying NK₂ receptor-mediated signaling. The binding affinity of Neurokinin A(4-10) at the NK₂ receptor is comparable to that of the full-length peptide, as the C-terminal region is critical for receptor recognition and activation.
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| ln Vitro |
The tachykinin NK2 receptor is the only mechanism by which neurokinin A (NKA) and its shortened form NKA(4–10), which are strong spasmodics of the circular muscle of the human colon, work. In order to determine the significance of amino acid residues for receptor efficacy, potency, and affinity for NK2 receptors in human colonic circular muscle, structure-activity studies were conducted on the neurokinin A (NKA) fragment NKA(4–10). Using in vitro autoradiography and radioligand binding, it has been shown that this tissue contains high densities of NK2 receptors [1].
In vitro, Neurokinin A(4-10) functions as a potent agonist at tachykinin NK₂ receptors. The peptide induces concentration-dependent contraction of smooth muscle preparations, particularly in the human colon, where it acts as a potent spasmogen. This contractile response is mediated exclusively through NK₂ receptor activation, as confirmed by studies using selective NK₂ receptor antagonists. In cell-based assays, Neurokinin A(4-10) stimulates NK₂ receptor-mediated signaling pathways, including phospholipase C activation, calcium mobilization, and MAP kinase phosphorylation. The peptide also exhibits activity in various other smooth muscle preparations, including the urinary bladder, uterus, and airways, reflecting the broad distribution of NK₂ receptors. Its potency in these assays typically ranges from nanomolar to sub-micromolar concentrations, depending on the tissue and species. |
| ln Vivo |
In vivo, Neurokinin A(4-10) has been extensively used to study the physiological and pathophysiological roles of NK₂ receptors. Administration of the peptide in animal models induces various effects including smooth muscle contraction, increased vascular permeability, and modulation of pain responses. The peptide has been studied in models of gastrointestinal motility disorders, asthma, and inflammatory diseases, where NK₂ receptor activation plays a significant role. However, due to its rapid enzymatic degradation in vivo, the peptide is typically administered locally or used in ex vivo tissue bath experiments rather than systemic administration. The truncated form NKA(4-10) has been shown to maintain the biological activity of the full-length peptide in these models, making it a useful tool for studying NK₂ receptor function in vivo.
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| Enzyme Assay |
For in vitro receptor binding studies, Neurokinin A(4-10) can be evaluated using radioligand binding assays with membranes prepared from cells expressing recombinant or native NK₂ receptors. A radiolabeled NK₂ receptor ligand, such as [³H]SR48968 or [¹²⁵I]Neurokinin A, is incubated with the membrane preparation and varying concentrations of the test peptide. After incubation, bound and free radioligand are separated by filtration or centrifugation, and radioactivity is counted. Competition binding curves are generated to determine the inhibition constant (Ki) of Neurokinin A(4-10) at the NK₂ receptor. For functional studies, GTPγS binding assays are performed to measure receptor activation. Membranes are incubated with [³⁵S]GTPγS, GDP, and varying concentrations of the peptide, and the amount of bound [³⁵S]GTPγS is measured to determine receptor-mediated G protein activation.
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| Cell Assay |
For in vitro cell-based assays, cells expressing recombinant NK₂ receptors (e.g., CHO cells stably transfected with human NK₂R) or cell lines naturally expressing NK₂ receptors are cultured in appropriate media. Cells are seeded in 96-well or 384-well plates and treated with Neurokinin A(4-10) at various concentrations. Functional responses are measured using calcium mobilization assays with fluorescent calcium indicators such as Fluo-4 or Fura-2. The peptide-induced increase in intracellular calcium is monitored using a fluorescence plate reader. For cell proliferation or migration assays, cells are treated with the peptide and cell number or migration is measured using standard techniques (MTT assay, transwell migration assay). Receptor internalization studies can be performed using fluorescently labeled Neurokinin A(4-10) and confocal microscopy.
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| Animal Protocol |
For in vivo animal studies, Neurokinin A(4-10) is typically administered locally due to its rapid enzymatic degradation. In models of gastrointestinal motility, the peptide can be injected intravenously or intraperitoneally, and gastrointestinal transit or colonic contractility is measured. In airway hyperreactivity models, the peptide is administered by aerosol or intravenous injection, and airway resistance or bronchoconstriction is measured. In pain models, intrathecal or intracerebroventricular administration is used to evaluate the role of NK₂ receptors in pain transmission. Blood pressure and heart rate are monitored to assess cardiovascular effects. The peptide can also be administered topically in models of inflammation to evaluate its effects on vascular permeability and edema formation.
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| ADME/Pharmacokinetics |
Dedicated pharmacokinetic studies of Neurokinin A(4-10) are limited due to its use as a research peptide rather than a therapeutic agent. As a small peptide, it is rapidly degraded by peptidases in the bloodstream and tissues, resulting in a very short half-life (typically minutes). The peptide is susceptible to cleavage by neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), which limits its systemic bioavailability. When administered locally, the peptide acts at the site of administration with minimal systemic exposure. The TFA salt form of the peptide (Neurokinin A(4-10) TFA) is often used to improve solubility and stability. For research purposes, the peptide is typically dissolved in aqueous buffers or saline and used immediately, as prolonged storage in solution may lead to degradation.
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| Toxicity/Toxicokinetics |
Neurokinin A(4-10) is a research peptide and is not used as a therapeutic agent. The peptide itself is not considered toxic at the concentrations used in research applications. However, as a potent NK₂ receptor agonist, it can induce biological effects including smooth muscle contraction, vasodilation, and increased vascular permeability at pharmacological doses. In animal studies, high doses may cause bronchoconstriction, hypotension, and gastrointestinal motility changes. The peptide is not intended for human use and standard laboratory safety precautions should be observed when handling. The TFA salt form may be irritating to the skin, eyes, and respiratory tract.
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| References | |
| Additional Infomation |
Neurokinin A(4-10) is primarily used as a research tool in neuropharmacology and gastrointestinal research. It is commercially available from various peptide suppliers for research purposes only and is not approved for therapeutic use. The peptide is valuable for studying the role of NK₂ receptors in various physiological and pathological processes, including pain transmission, smooth muscle contraction, inflammation, and cancer. The truncated form NKA(4-10) retains the full biological activity of the parent peptide while being more amenable to chemical synthesis. It is commonly used in conjunction with selective NK₂ receptor antagonists to study receptor-mediated signaling pathways. The peptide serves as a useful tool for validating NK₂ receptor targets in drug discovery programs aimed at developing novel therapeutics for gastrointestinal disorders, asthma, and pain.
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| Molecular Formula |
C34H54N8O10S
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| Molecular Weight |
766.905160000001
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| Exact Mass |
766.368
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| CAS # |
97559-35-8
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| Related CAS # |
Neurokinin A(4-10) TFA
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| PubChem CID |
122230
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.276g/cm3
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| Boiling Point |
1231.2ºC at 760mmHg
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| Flash Point |
698.4ºC
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| Index of Refraction |
1.565
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| LogP |
1.25
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
53
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| Complexity |
1260
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| Defined Atom Stereocenter Count |
6
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| SMILES |
[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(=O)O)(C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N)CCSC)CC1C=CC=CC=1
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| InChi Key |
YLVSTHFZZCHRCL-ORUZXOCWSA-N
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| InChi Code |
InChI=1S/C34H54N8O10S/c1-18(2)13-23(31(49)39-22(29(36)47)11-12-53-5)38-26(44)16-37-34(52)28(19(3)4)42-32(50)24(14-20-9-7-6-8-10-20)40-33(51)25(17-43)41-30(48)21(35)15-27(45)46/h6-10,18-19,21-25,28,43H,11-17,35H2,1-5H3,(H2,36,47)(H,37,52)(H,38,44)(H,39,49)(H,40,51)(H,41,48)(H,42,50)(H,45,46)/t21-,22-,23-,24-,25-,28-/m0/s1
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| Chemical Name |
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3039 mL | 6.5197 mL | 13.0393 mL | |
| 5 mM | 0.2608 mL | 1.3039 mL | 2.6079 mL | |
| 10 mM | 0.1304 mL | 0.6520 mL | 1.3039 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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