MRS-1191
目录号 : GC38112
MRS-1191 是一种有效的选择性的 A3 腺苷受体 (A3 adenosine receptor ) 拮抗剂，其 KB 值为 92 nM，对人 A3 受体的 Ki 值为 31.4 nM，对 CHO 细胞的 IC50 值为 120 nM。
Cas No.:185222-90-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MRS-1191 is a potent and selective A3 adenosine receptor antagonist with a KB value of 92 nM, a Ki value of 31.4 nM for human A3 receptor and an IC50 of 120 nM for CHO cells[1].
The effects of putative A3 adenosine receptor antagonist of MRS-1191 is characterized in receptor binding and functional assays. MRS-1191 is found to be competitive in saturation binding studies using the agonist radioligand [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide) at cloned human brain A3 receptor expressed in HEK-293 cells. Antagonism is demonstrated in functional assays consisting of agonist-induced inhibition of adenylate cyclase and the stimulation of binding of [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTP-gamma-S) to the associated G-proteins. MRS-1191 with a KB value of 92 nM, proves to be highly selective for human A3 receptor vs human A1 receptor-mediated effects on adenylate cyclase[1].
[1]. Jacobson KA, et al. Pharmacological characterization of novel A3 adenosine receptor-selective antagonists. Neuropharmacology. 1997 Sep;36(9):1157-65.
| Cas No. | 185222-90-6 | SDF | |
| Canonical SMILES | O=C(OCC)C1=C(NC(C2=CC=CC=C2)=C(C1C#CC3=CC=CC=C3)C(OCC4=CC=CC=C4)=O)C | ||
| 分子式 | C31H27NO4 | 分子量 | 477.55 |
| 溶解度 | DMSO: 250 mg/mL (523.51 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.094 mL | 10.4701 mL | 20.9402 mL |
| 5 mM | 0.4188 mL | 2.094 mL | 4.188 mL |
| 10 mM | 0.2094 mL | 1.047 mL | 2.094 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A3 adenosine receptor inhibition improves the efficacy of hypertonic saline resuscitation
Shock 2011 Feb;35(2):178-83.PMID:20661181DOI:10.1097/SHK.0b013e3181f221fb.
We reported previously that hypertonic saline (HS) treatment can prevent or upregulate the function of polymorphonuclear neutrophils (PMNs) via A2a-type adenosine receptors or A3-type adenosine receptors (A3R), respectively. A3R translocate to the cell surface upon PMN stimulation, and thus, HS promotes PMN responses under conditions of delayed HS treatment. Here we investigated if inhibition of A3R improves the protective effects of HS resuscitation in a mouse sepsis model. We found that HS nearly triples extracellular adenosine concentrations in whole blood and that inhibition of A3R with the selective antagonist MRS-1191 dose dependently improves the inhibitory effect of HS. MRS-1191 at a concentration of 1 nM enhanced the inhibitory effect of HS and reduced stimulatory effects of delayed HS treatment. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found that MRS-1191 reduces acute lung injury and PMN accumulation in lung tissue. Whereas delayed HS treatment (4 mL/kg of 7.5% NaCl) of mice 1 h after CLP aggravated PMN accumulation, lung tissue damage, and mortality 24 h after CLP, infusion of MRS-1191 (2 ng/kg body weight) combined with HS reduced these detrimental effects of delayed HS treatment. Our data thus show that A3 receptor antagonists can strengthen the beneficial effects of HS resuscitation by avoiding stimulatory adverse effects that result from delayed HS administration.
Effect of endogenous purines on electrically evoked ACh release at the mouse neuromuscular junction
J Neurosci Res 2022 Oct;100(10):1933-1950.PMID:35839285DOI:10.1002/jnr.25107.
At the mouse neuromuscular junction, adenosine triphosphate (ATP), which is co-released with the neurotransmitter acetylcholine (ACh), and its metabolite adenosine, modulate neurotransmitter release by activating presynaptic inhibitory P2Y<sub>13</sub> receptors (a subtype of ATP/adenosine diphosphate [ADP] receptor), inhibitory A<sub>1</sub> and A<sub>3</sub> adenosine receptors, and excitatory A<sub>2A</sub> adenosine receptors. To study the effect of endogenous purines, when phrenic-diaphragm preparations are depolarized by different nerve stimulation patterns, we analyzed the effect of the antagonists for P2Y<sub>13</sub> , A<sub>1</sub> , A<sub>3</sub> , and A<sub>2A</sub> receptors (AR-C69931MX, 8-cyclopentyl-1,3-dipropylxanthine, MRS-1191, and SCH-58261, respectively) on the amplitude of the end-plate potentials of the trains, and contrasted these results with those obtained with the selective agonists of these receptors (2-methylthioadenosine 5'-diphosphate trisodium salt hydrate, 2-chloro-N<sup>6</sup> -cyclopentyl-adenosine, inosine, and PSB-0777, respectively). During continuous 0.5-Hz stimulation, the amount of endogenous purines was not enough to activate purinergic receptors, while at continuous 5-Hz stimulation, an incipient action of endogenous purines on P2Y<sub>13</sub> , A<sub>1</sub> and A3 receptors might be evident just at the end of the trains. During continuous 50-Hz stimulation, the concentration of endogenous ATP/ADP and adenosine exerted an inhibitory action on ACh release after of the initial phase of the train, but when the nerve was stimulated at intermittent 50 Hz (5 bursts), this behavior was not observed. Excitatory A<sub>2A</sub> receptors were only activated when continuous 100-Hz stimulation was applied. In conclusion, when motor nerve terminals are depolarized by repetitive stimulation of the phrenic nerve, endogenous ATP/ADP and adenosine are able to fine-tune neurosecretion depending on the frequency and pattern of stimulation.
Endogenous purines modulate K+ -evoked ACh secretion at the mouse neuromuscular junction
J Neurosci Res 2018 Jun;96(6):1066-1079.PMID:29436006DOI:10.1002/jnr.24223.
At the mouse neuromuscular junction, adenosine triphosphate (ATP) is co-released with the neurotransmitter acetylcholine (ACh), and once in the synaptic cleft, it is hydrolyzed to adenosine. Both ATP/adenosine diphosphate (ADP) and adenosine modulate ACh secretion by activating presynaptic P2Y13 and A1 , A2A , and A3 receptors, respectively. To elucidate the action of endogenous purines on K+ -dependent ACh release, we studied the effect of purinergic receptor antagonists on miniature end-plate potential (MEPP) frequency in phrenic diaphragm preparations. At 10 mM K+ , the P2Y13 antagonist N-[2-(methylthio)ethyl]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with (dichloromethylene)bis[phosphonic acid], tetrasodium salt (AR-C69931MX) increased asynchronous ACh secretion while the A1 , A3 , and A2A antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), (3-Ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(±)-dihydropyridine-3,5-, dicarboxylate (MRS-1191), and 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH-58261) did not modify neurosecretion. The inhibition of equilibrative adenosine transporters by S-(p-nitrobenzyl)-6-thioinosine provoked a reduction of 10 mM K+ -evoked ACh release, suggesting that the adenosine generated from ATP is being removed from the synaptic space by the transporters. At 15 and 20 mM K+ , endogenous ATP/ADP and adenosine bind to inhibitory P2Y13 and A1 and A3 receptors since AR-C69931MX, DPCPX, and MRS-1191 increased MEPP frequency. Similar results were obtained when the generation of adenosine was prevented by using the ecto-5'-nucleotidase inhibitor α,β-methyleneadenosine 5'-diphosphate sodium salt. SCH-58261 only reduced neurosecretion at 20 mM K+ , suggesting that more adenosine is needed to activate excitatory A2A receptors. At high K+ concentration, the equilibrative transporters appear to be saturated allowing the accumulation of adenosine in the synaptic cleft. In conclusion, when motor nerve terminals are depolarized by increasing K+ concentrations, the ATP/ADP and adenosine endogenously generated are able to modulate ACh secretion by sequential activation of different purinergic receptors.
Cardioprotective effects of 2-octynyladenosine (YT-146) in ischemic/reperfused rat hearts
J Cardiovasc Pharmacol 2011 Feb;57(2):166-73.PMID:21052018DOI:10.1097/FJC.0b013e318201c264.
The present study was aimed at investigating the cardiac receptor subtypes involved in the cardioprotective effects of 2-octynyladenosine (YT-146), a novel adenosine receptor (AR) agonist. Isolated rat hearts were perfused in the Langendorff manner, and the hearts were exposed to 30 minute of ischemia followed by 60 minutes of reperfusion. YT-146 was infused for 10 minutes just before ischemia, and selective antagonists for AR subtypes were coadministered with YT-146. YT-146 (0.03–0.3 μM) dose dependently improved postischemic recovery of the left ventricular developed pressure (LVDP) of the ischemic/reperfused rat heart (maximum 59.7% ± 2.3% of the preischemic value). Coadministration of 8-(3-chlorostyryl) caffeine (A(2A) AR antagonist), alloxazine (A(2B)AR antagonist), or MRS-1191 (A(3) AR antagonist) with YT-146 failed to alter the cardioprotective effects of YT-146, and their LVDP recoveries were 55.9% ± 5.1%, 52.1% ± 1.9%, and 47.5% ± 1.7%, respectively, at the end of the reperfusion. On the other hand, coadministration of 8-cyclopentyl-1,3-dipropylxanthine (A(1) AR antagonist) abolished the YT-146–induced enhancement of postischemic LVDP recovery (31.7% ± 4.6%). The protein kinase C inhibitor chelerythrine also abolished the YT-146–induced enhancement of postischemic LVDP recovery (22.2% ± 4.5%). YT-146 has been known as an A(2) AR agonist, but our findings suggest that the cardioprotective effects of YT-146 are exerted via cardiac A(1) AR, not A(2) AR, stimulation and the activation of protein kinase C by preischemic treatment in isolated and crystalloid-perfused rat hearts.
Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models
Korean J Anesthesiol 2019 Feb;72(1):60-67.PMID:29969887DOI:10.4097/kja.d.18.00022.
Background: The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. Methods: Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. Results: Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. Conclusions: The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.