| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Mechanosensitive channels/MSCs
D-GsMTx4 TFA targets mechanosensitive ion channels (MSCs), specifically the Piezo1 and Piezo2 channels. It also inhibits cation-permeable stretch-activated channels (SACs) and channels belonging to the TRP family. Its mechanism of action is unique; it does not block the channel pore directly but rather partitions into the lipid bilayer and modifies the mechanical properties of the membrane, thereby inhibiting channel gating. This "membrane-mediated" mechanism of action is distinct from conventional ion channel blockers and contributes to its selectivity. |
|---|---|
| ln Vitro |
D-GsMTx4 inhibition of QGP-1 cell mechanosensitive currents is dose-dependent.[1]
D-GsMTx4 blocks heterologously expressed Piezo2 currents in HEK-293 cells.[1] Enterochromaffin (EC) cells are the primary mechanosensors of the gastrointestinal (GI) epithelium. In response to mechanical stimuliEC cells release serotonin (5-hydroxytryptamine; 5-HT). The molecular details ofEC cell mechanosensitivity are poorly understood. Recently, our group found that human and mouseEC cells express the mechanosensitive ion channel Piezo2. The mechanosensitive currents in a humanEC cell model QGP-1 were blocked by the mechanosensitive channel blocker D-GsMTx4. In the present study we aimed to characterize the effects of the mechanosensitive ion channel inhibitor spider peptide D-GsMTx4 on the mechanically stimulated currents from both QGP-1 and human Piezo2 transfected HEK-293 cells. We found co-localization of 5-HT and Piezo2 in QGP-1 cells by immunohistochemistry. QGP-1 mechanosensitive currents had biophysical properties similar to dose-dependently Piezo2 and were inhibited by D-GsMTx4. In response to direct displacement of cell membranes, human Piezo2 transiently expressed in HEK-293 cells produced robust rapidly activating and inactivating inward currents. D-GsMTx4 reversibly and dose-dependently inhibited both the potency and efficacy of Piezo2 currents in response to mechanical force. Our data demonstrate an effective inhibition of Piezo2 mechanosensitive currents by the spider peptide D-GsMTx4.[1] In vitro, D-GsMTx4 TFA selectively inhibits Piezo1 and Piezo2 channels with high potency. It blocks mechanosensitive currents in cells expressing these channels. The D-enantiomer shows improved stability compared to the L-form while maintaining similar inhibitory activity. It also attenuates lysophosphatidylcholine (LPC)-induced astrocyte toxicity and microglia reactivity, indicating its potential to modulate cellular responses to mechanical stress. |
| ln Vivo |
D-GsMTx4 TFA has been used in animal models to study the role of mechanosensitive channels in pain, cardiovascular function, and other mechanotransduction-related processes. Its enhanced stability makes it suitable for in vivo applications where proteolytic degradation is a concern. While specific in vivo efficacy data are not detailed in the provided sources, its ability to inhibit mechanosensitive channels has been leveraged to study their physiological and pathophysiological roles.
|
| Enzyme Assay |
Non-cellular assays for D-GsMTx4 TFA are not typically performed as it targets ion channels that require a lipid bilayer and a membrane environment for proper function. Its mechanism of action involves interaction with the lipid membrane, which cannot be recapitulated in a simple cell-free system. Its activity is assessed in electrophysiological studies using cells expressing the target channels.
|
| Cell Assay |
The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine; 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5-HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically-sensitive inward non-selective cation current characteristic of Piezo2. Both inward currents and 5-HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D-GsMTx4). Jejunum mucosal pressure increased 5-HT release and short-circuit current via submucosal 5-HT3 and 5-HT4 receptors. Pressure-induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D-GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects[2].
In vitro cellular assays for D-GsMTx4 TFA are performed using cells that express mechanosensitive channels, such as Piezo1 or Piezo2. Patch-clamp electrophysiology is the gold standard technique used to measure the inhibition of mechanosensitive currents. Cells are mechanically stimulated (e.g., by membrane stretch or pressure application), and the resulting currents are recorded in the presence and absence of the peptide. Dose-response curves are generated to determine IC50 values for channel inhibition. |
| Animal Protocol |
In vivo animal experiments for D-GsMTx4 TFA involve administering the peptide to animal models, typically mice. Dosing routes may include intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection, depending on the target tissue and the specific research question. Its effects on pain behavior, cardiovascular parameters, or other mechanosensation-related endpoints are then assessed.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties: D-GsMTx4 TFA, being a D-amino acid peptide, exhibits enhanced resistance to proteolytic degradation compared to L-peptides. This improved stability may result in a longer half-life and better bioavailability for in vivo studies. Specific PK parameters, such as half-life and clearance, are not detailed in the available sources.
|
| Toxicity/Toxicokinetics |
Toxicological data for D-GsMTx4 TFA are not provided in the available sources. As a research peptide, its safety profile has not been extensively characterized. It is intended for research use only and not for human consumption.
|
| References | |
| Additional Infomation |
D-GsMTx4 TFA is a D-amino acid enantiomer of the spider venom peptide GsMTx4. It is a selective inhibitor of mechanosensitive ion channels, including Piezo1 and Piezo2. Its enhanced stability makes it a valuable tool for studying mechanotransduction in vivo. It is not approved for clinical use.
|
| Molecular Formula |
C185H273N49O45S6.XC2HF3O2
|
|---|---|
| Molecular Weight |
4095.84 (free base)
|
| Exact Mass |
4095.84 (free base)
|
| Related CAS # |
GsMTx4;1209500-46-8;GsMTx4 TFA;D-GsMTx4
|
| Appearance |
White to off-white 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) |
DMSO :~100 mg/mL
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
