| Targets |
beta-CGRP (mouse) targets the CGRP receptor, a heterodimer composed of a calcitonin-like receptor (CLR) and a receptor activity-modifying protein 1 (RAMP1). This complex specifically recognizes CGRP. The primary function of this receptor is to transduce signals leading to vasodilation, pro-inflammatory cytokine release (e.g., in neurogenic inflammation), and sensory neurotransmission (especially pain and migraine).
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| ln Vitro |
In vitro, beta-CGRP (mouse) (0.1-100 nM) is a potent vasodilator, relaxing pre-constricted arteries such as the rat coronary artery and middle meningeal artery (relevant to migraine pathophysiology). It increases intracellular cAMP levels in cells expressing the CLR/RAMP1 receptor. It has a vasorelaxant effect in the artery of WT (RAMP1+/+) mice, whereas alphaCGRP has less effect. In rat bone marrow cells, CGRP receptors exhibit affinity (Kᵢ) of 0.899 and 0.711 nM for rat alphaCGRP and betaCGRP, respectively.
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| ln Vivo |
In vivo, CGRP is a potent vasodilator, with both isoforms increasing blood flow in numerous tissues, including the heart, kidney, and skin. In mouse models, beta-CGRP is essential for normal cardiovascular function, blood pressure regulation, and may play a role in cardiovascular development. The expression patterns of CGRP isoforms in spinal cord motor neurons of SOD1G93A mice (an ALS model) show pathology-related changes, suggesting the potential involvement of beta-CGRP in ALS.
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| Enzyme Assay |
For CGRP receptor binding assays, membrane preparations from rat or mouse brain (cerebellum, hypothalamus) or cells expressing recombinant CLR/RAMP1 are incubated with 0.05-0.2 nM [¹2⁵I]-beta-CGRP (specific activity 2000 Ci/mmol) and increasing concentrations (0.01-1000 nM) of unlabeled beta-CGRP (mouse) in 50 mM HEPES (pH 7.4), 5 mM MgCl2, 0.1% BSA for 90 min at 25degC. Non-specific binding is determined with 1 uM unlabeled beta-CGRP. Bound radioactivity is separated by filtration through GF/B filters and counted in a gamma counter. Kᵢ is calculated. For cAMP assays, cells expressing CLR/RAMP1 are seeded in 96-well plates, treated with beta-CGRP (0.01-1000 nM) and 0.5 mM IBMX (to inhibit phosphodiesterase) for 15 min, and cAMP is measured by ELISA (EC₅0 typically 0.1-10 nM). For isolated artery vasodilation studies, mouse coronary arteries are dissected and mounted on a wire myograph in Krebs buffer with 95% O2/5% CO2 at 37degC. Vessels are pre-constricted with 1 uM U46619 or 60 mM KCl, and cumulative doses of beta-CGRP (0.1-100 nM) are added. Vasodilation is recorded (as % relaxation) using PowerLab data acquisition. The CGRP antagonist CGRP8-37 (1 uM) is added 15 minutes before beta-CGRP to block the response. For primary bone marrow cell cultures, isolated mouse bone marrow cells are treated with 0.1-100 nM beta-CGRP for 15 minutes, and cAMP levels are measured by ELISA.
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| Cell Assay |
For microglial activation assays, primary mouse microglia or BV-2 cells are treated with beta-CGRP (1-100 nM) for 6-24 h. Pro-inflammatory cytokine release (TNF-alpha, IL-6, IL-1beta) is measured by ELISA, and NF-kappaB signaling is assessed by Western blot (p65 phosphorylation). For isolated cardiomyocytes, neonatal rat ventricular myocytes (NRVMs) are treated with beta-CGRP (1-100 nM) for 10-30 minutes; cell size (hypertrophy) is assessed by alpha-actinin immunostaining, and contractility is measured using video edge detection. For in vivo cardiovascular studies, male C57BL/6 mice (8-10 weeks, n=8-10) are anesthetized (isoflurane), and a catheter is placed in the carotid artery to monitor mean arterial pressure (MAP). beta-CGRP (mouse) (1-30 ug/kg in saline) is administered via intrajugular or intra-arterial injection. MAP is recorded for 30-60 minutes. A decrease in MAP indicates vasodilation (e.g., 5-20% reduction from baseline). This effect is blocked by CGRP8-37 (1 mg/kg). For a blood flow study, C57BL/6 mice are placed under a laser Doppler perfusion imager; beta-CGRP (1-10 ug/kg) is injected intravenously, and hindlimb or cerebral blood flow is measured. For an ALS (SOD1G93A) model, peptide is administered intrathecally (0.1-1 ug/day for 4-8 weeks) via mini-osmotic pump (Alzet). Motor function is assessed by rotarod and grip strength tests weekly; lumbar spinal cords are collected for immunohistochemistry (CGRP, choline acetyltransferase). For pain/migraine studies, beta-CGRP is injected intravenously or locally (e.g., periorbital region) in mice to induce pain behaviors (e.g., facial grimace, hind paw withdrawal threshold). RAMP1 knockout mice (RAMP1-/-) show no response to CGRP, confirming specificity. All animal procedures require IACUC approval.
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| ADME/Pharmacokinetics |
beta-CGRP is a 37-residue peptide (MW ~3786 g/mol) with a disulfide bond (Cys2-Cys7). It is soluble in water and PBS. After IV administration in mice, plasma half-life (t½) is short (5-10 min) due to rapid proteolysis (peptidases such as neutral endopeptidase 24.11 (NEP)). It is cleared by the kidneys. Infusion or continuous delivery (e.g., via osmotic pump) is required for sustained exposure. Not orally bioavailable.
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| Toxicity/Toxicokinetics |
beta-CGRP is a neuropeptide, generally non-toxic at low concentrations (nM). At high doses (>1 mg/kg IV), transient hypotension and tachycardia may occur. Not genotoxic.
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| References |
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| Additional Infomation |
beta-CGRP (mouse) is a research-grade peptide for CGRP signaling studies. CGRP receptor antagonists (e.g., erenumab, galcanezumab) are FDA-approved for migraine prevention. However, the peptide itself is not an approved drug and has no clinical trials. For research use only.
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| Appearance |
White to off-white solid powder
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| Synonyms |
Calcitonin gene-related peptide 2 (mouse); CGRP II (mouse)
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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 Note: (1). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O : ≥ 100 mg/mL (~25.78 mM)
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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.) |
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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