p2x1 Receptor P2X3 Receptor P2X7 Receptor

[1]. Overexpression of P2X3 and P2X7 Receptors and TRPV1 Channels in Adrenomedullary Chromaffin Cells in a Rat Model of Neuropathic Pain. Int J Mol Sci. 2019 Jan 3;20(1).

[2]. Activation and regulation of purinergic P2X receptor channels. Pharmacol Rev. 2011 Sep;63(3):641-83.

Adenosine 5'-[α,β-methylene]triphosphate is a nucleoside triphosphate analog. We tested the hypothesis that neuropathic pain serves as a stressor driving the functional plasticity of the sympathetic-adrenal system. Using behavioral, immunohistochemical, and electrophysiological techniques, we investigated the relationship between neuropathic pain and adrenal medullary function in rats with chronic sciatic nerve compression injury. In adrenal sections from animals with neuropathic pain, we observed increased cholinergic innervation and spontaneous synaptic activity at the visceral nerve-chromaffin junction. Similarly, adrenal medullary chromaffin cells exhibited increased acetylcholine-induced currents, enhanced sensitivity to α-conotoxin RgIA (a drug that selectively blocks nicotinic acetylcholine receptors containing the α9 subunit), and enhanced exocytosis triggered by voltage-activated Ca2+ influx. In summary, these adaptive changes are expected to promote the release of catecholamines into the bloodstream. Finally, and most notably, functional and immunohistochemical data showed that P2X3 and P2X7 purinergic receptors and transient receptor potential vanillic acid receptor 1 (TRPV1) channels were overexpressed in chromaffin cells of animals with neuropathic pain. These observations are similar to the characteristic molecular changes of peripheral sensitization of nociceptors after peripheral nerve injury, suggesting that similar phenomena may occur in other tissues and may lead to behavioral manifestations of neuropathic pain. [1]

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Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, named P2X1 through P2X7. Each subunit contains a large extracellular domain, two transmembrane domains, and an intracellular N-terminus and C-terminus. Functional P2XRs exist in the form of homotrimers and heterotrimers. This article reviews the binding sites involved in the activation (ortho- and allosteric) and regulation (alloyal) of P2XRs. The extracellular domain contains three ATP binding sites, presumably located between adjacent subunits and formed by highly conserved residues. The detection and coordination of positively charged amino acids to the three ATP phosphate residues may play a dominant role in determining agonist potency, while the AsnPheArg motif may facilitate binding by coordinating adenine rings. Non-conserved extracellular domain histidine residues provide binding sites for trace metals, divalent cations, and protons. The transmembrane domain is responsible not only for the formation of channel pores but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N-terminal and C-terminal domains constitute the structures that determine receptor desensitization and/or pore expansion dynamics and are crucial for regulating receptor function by substances such as intracellular messengers, kinases, reactive oxygen species, and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R channel in the closed state has greatly enhanced our understanding of this receptor channel family. We will combine the crystal structure with a large amount of site-directed mutagenesis data accumulated over the past 15 years to provide a structural explanation of the molecular basis of ortho- and allosteric ligand action. [2]

C11H15N5NA3O12P3

571.153697252274

570.962

1343364-54-4

90488813

White to off-white solid powder

4

16

8

34

781

4

C([C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C(N)N=CN=C32)O1)O)O)OP(=O)(CP(=O)([O-])OP(=O)(O)[O-])[O-].[Na+].[Na+].[Na+]

CBAGKCWFSRTVER-MTQUBGKESA-K

InChI=1S/C11H18N5O12P3.3Na/c12-9-6-10(14-2-13-9)16(3-15-6)11-8(18)7(17)5(27-11)1-26-29(19,20)4-30(21,22)28-31(23,24)25;;;/h2-3,5,7-8,11,17-18H,1,4H2,(H,19,20)(H,21,22)(H2,12,13,14)(H2,23,24,25);;;/q;3*+1/p-3/t5-,7-,8-,11-;;;/m1.../s1

trisodium;[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-[[[hydroxy(oxido)phosphoryl]oxy-oxidophosphoryl]methyl]phosphinate

1343364-54-4; ALPHA,BETA-METHYLENEADENOSINE 5'-TRIPHOSPHATE TRISODIUM SALT; Trisodium;[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-[[[hydroxy(oxido)phosphoryl]oxy-oxidophosphoryl]methyl]phosphinate; alpha,beta-Methyleneadenosine5'-TriphosphateTrisodiumSalt;

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 125 mg/mL (218.86 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)