| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
The rat PTH(1-34) peptide specifically targets the parathyroid hormone 1 receptor (PTH1R), a class B GPCR expressed mainly in bone (osteoblasts) and kidney (distal tubules). As a full agonist, it binds to PTH1R and activates Gs-adenylyl cyclase-cAMP-PKA signaling and Gq-phospholipase C-PKC pathways. PTH(1-34) stimulation of osteoblasts increases expression of RANKL, leading to increased bone resorption, but anabolic (bone-forming) effects depend on intermittent administration, whereas continuous exposure causes bone loss.
|
|---|---|
| ln Vitro |
In primary rat osteoblast cultures or UMR-106 rat osteosarcoma cells, rat PTH(1-34) acetate (0.1-100 nM) stimulates cAMP production in a concentration-dependent manner, with an EC50 of approximately 1-10 nM. The peptide (10-100 nM) also induces alkaline phosphatase activity and osteoblast differentiation markers (Runx2, osteocalcin, collagen I). In rat osteoclast precursor cultures, PTH(1-34) indirectly enhances osteoclastogenesis through increased RANKL/OPG ratio in osteoblasts.
|
| ln Vivo |
In rats, parathyroid hormone (1-34) (acetate) (sc; 40 mg/kg; daily; for 4 weeks) stimulates bone formation[1].
In rat models of osteoporosis (e.g., ovariectomized rats), subcutaneous injection of rat PTH(1-34) acetate (40 microg/kg daily for 4 weeks) significantly improves both cortical and cancellous bone structure, increasing bone mineral density (BMD) and trabecular thickness. The anabolic effect of intermittent PTH is well established: daily injections stimulate bone formation, while continuous infusion leads to catabolic effects. Histomorphometric analysis shows increased osteoblast surface and mineral apposition rate (MAR). |
| Enzyme Assay |
For receptor binding assays: membranes from COS-7 or HEK293 cells transfected with rat PTH1R are incubated with ¹2⁵I-labeled [Nle⁸,¹⁸,Tyr3⁴]rat PTH(1-34) (50,000 cpm) in binding buffer (50 mM Tris-HCl, pH 7.7, 100 mM NaCl, 2 mM CaCl2, 0.1% BSA, 0.25 mg/mL bacitracin) with increasing concentrations (0.01-1000 nM) of unlabeled rat PTH(1-34) acetate for 2 hours at 25degC. Bound radioligand is separated by filtration through GF/C filters pre-soaked in 0.5% polyethylenimine. Radioactivity is measured by gamma counter. Competitive binding curves are analyzed by GraphPad Prism.
|
| Cell Assay |
Functional activation assays are performed in UMR-106 rat osteosarcoma cells (passage 15-20) or primary rat osteoblasts (isolated from neonatal rat calvaria, passages 2-3). Cells are seeded in 96-well plates (2×10⁴ cells/well) in alpha-MEM + 10% FBS for 24-48 h. Cells are washed twice with HBSS and incubated with rat PTH(1-34) acetate (0.01-1000 nM) diluted in HBSS containing 1 mM IBMX (a phosphodiesterase inhibitor) for 15 min at 37degC. The reaction is terminated by adding 0.1 M HCl. The lysate is neutralized, and cAMP levels are quantified using a competitive ELISA kit (cAMP EIA) according to the manufacturer's instructions. The optical density (405 nm) is converted to cAMP concentration (pmol/mL) using a standard curve. EC50 values are calculated from dose-response curves. For differentiation assays, cells are treated with PTH(1-34) (1-100 nM) in differentiation medium (alpha-MEM + 10% FBS, 50 microg/mL ascorbic acid, 10 mM beta-glycerophosphate) for 7-14 days. Medium is changed every 2-3 days. Alkaline phosphatase (ALP) activity is measured using a colorimetric assay (p-nitrophenyl phosphate substrate, absorbance at 405 nm). Mineralization is assessed by Alizarin Red S staining (absorbance at 550 nm) after 14-21 days. Runx2, Bglap (osteocalcin), and Col1a1 mRNA levels are quantified by qRT-PCR.
|
| Animal Protocol |
Animal/Disease Models: ovariectomized (Ovx) rats[1]
Doses: 40 mg/kg Route of Administration: sc, per day, for 4 weeks Experimental Results: Preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Shamooperated animals. Prevented further loss of connectivity and Cn-BV/TV, and combined estrogen and PTH resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. Adult female Sprague-Dawley rats (3-6 months old, 200-250 g) are ovariectomized (OVX) or sham-operated. After 4-8 weeks (to establish established osteopenia), rats (n=10 per group) receive daily subcutaneous injections (alternating sides of the dorsal neck) of rat PTH(1-34) acetate (40 microg/kg per day, dissolved in 0.9% saline with 0.1% BSA, pH 4.5) or vehicle (0.9% saline with 0.1% BSA) for 4-8 weeks. Calcein (15 mg/kg, i.p.) is administered 10 days and 3 days before sacrifice for dynamic histomorphometry. At the end of the study, rats are euthanized. The right femur and L4-L5 vertebrae are excised, cleaned of soft tissue, and fixed in 70% ethanol. BMD is measured by dual-energy X-ray absorptiometry (DXA) or micro-CT. Bones are embedded in methyl methacrylate for histomorphometry. Undecalcified sections (5 um) are cut and stained with von Kossa or toluidine blue for bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS). Serum osteocalcin (bone formation marker) and C-terminal telopeptide of type I collagen (CTX-1, bone resorption marker) are measured by ELISA. |
| ADME/Pharmacokinetics |
The pharmacokinetics of rat PTH(1-34) have been studied in rats. After subcutaneous administration at 40 microg/kg, the peptide is rapidly absorbed with a Tmax of 15-30 minutes. Peak plasma concentration (Cmax) is approximately 10-20 ng/mL. The elimination half-life (t1/2) is short, approximately 20-30 minutes, due to rapid degradation by endopeptidases in the liver and kidney. The absolute bioavailability of subcutaneous PTH in rats is approximately 50-60%. The compound is distributed primarily to bone and kidney. The acetate salt does not significantly alter the PK compared to the free base or hydrochloride salt.
|
| Toxicity/Toxicokinetics |
PTH(1-34) (rat) acetate is used at species-specific doses and has a wide therapeutic window based on its mechanism. In rat studies, daily administration at 40 microg/kg (subcutaneous) for 4-8 weeks is well-tolerated without significant adverse events. Higher doses (≥200 microg/kg) may cause hypercalcemia (elevated serum calcium), weight loss, and lethargy. Long-term treatment (≥6 months) may lead to osteosarcoma, but this has been observed primarily in rat toxicology studies with the human PTH analog teriparatide and is a species-specific response. The mechanism-based risk of osteosarcoma in rats is not considered directly translatable to humans. No other organ toxicities are reported.
|
| References |
|
| Additional Infomation |
Rat PTH(1-34) is a research-grade peptide and is not approved for human therapy. For human therapeutic use, the human sequence (teriparatide) is FDA-approved. The rat sequence provides more accurate pharmacology in rat disease models compared to using human PTH(1-34), which has lower potency at the rat PTH1R due to sequence differences. The acetate salt improves solubility and stability. Store as a lyophilized powder at -20degC for up to 2 years. Reconstitute in sterile water or 0.1% acetic acid to 1-10 mg/mL; working solutions should be diluted in 0.9% saline containing 0.1% BSA for in vivo administration. The peptide is prone to aggregation; avoid repeated freeze-thaw cycles.
|
| Molecular Formula |
C182H295N55O50S2
|
|---|---|
| Molecular Weight |
4117.76
|
| Related CAS # |
Parathyroid hormone (1-34) (rat);98614-76-7
|
| Appearance |
Solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O :≥ 100 mg/mL (~24.29 mM)
|
|---|---|
| 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 | 0.2429 mL | 1.2143 mL | 2.4285 mL | |
| 5 mM | 0.0486 mL | 0.2429 mL | 0.4857 mL | |
| 10 mM | 0.0243 mL | 0.1214 mL | 0.2429 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
