Sp-cAMPS
目录号 : GC61747
Sp-cAMPS，一种cAMP类似物，是一种依赖cAMP的PKAI和PKAII的有效激活剂。Sp-cAMPS还是一种有效的竞争性磷酸二酯酶(PDE3A)抑制剂，Ki为47.6µM。Sp-cAMPS以EC50为40μM来结合PDE10GAF域。
Cas No.:71774-13-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sp-cAMPS, a cAMP analog, is potent activator of cAMP-dependent PKA I and PKA II. Sp-cAMPS is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a Ki of 47.6 µM. Sp-cAMPS binds the PDE10 GAF domain with an EC50 of 40 μM[1][2][3].
Treatment of hepatocytes with Sp-cAMPS, the stimulatory diastereomer of adenosine cyclic 3',5'-phosphorothioate, mimics the response seen with glucagon. The glucagon-stimulated increases in the level of Ca2+ can be mimicked by Sp-cAMPS[4].
In chronic alcohol consumption (CAC) mice, direct infusion of the Sp-cAMPS (1 µg/µL) into the prefrontal cortex significantly improves or impairs, respectively, working memory performance in withdrawn and water animals[5].
[1]. Su H Hung, et al. A new nonhydrolyzable reactive cAMP analog, (Sp)-adenosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate irreversibly inactivates human platelet cGMP-inhibited cAMP phosphodiesterase. Bioorg Chem. 2002 Feb;30(1):16-31. [2]. L Y Wang, et al. Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science. 1991 Sep 6;253(5024):1132-5. [3]. Ronald JÄger, et al. Activation of PDE10 and PDE11 phosphodiesterases. J Biol Chem. 2012 Jan 6;287(2):1210-9. [4]. P A Connelly,et al. A study of the mechanism of glucagon-induced protein phosphorylation in isolated rat hepatocytes using (Sp)-cAMPS and (Rp)-cAMPS, the stimulatory and inhibitory diastereomers of adenosine cyclic 3',5'-phosphorothioate. J Biol Chem. 1987 Mar 25;262(9):4324-32. [5]. G Dominguez, et al. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure. Brain Struct Funct. 2016 Mar;221(2):865-77.
| Cas No. | 71774-13-5 | SDF | |
| Canonical SMILES | O[C@H]1[C@@H](O[C@@]2([H])[C@@]1([H])O[P@](OC2)(S)=O)N3C4=C(C(N)=NC=N4)N=C3 | ||
| 分子式 | C10H12N5O5PS | 分子量 | 345.27 |
| 溶解度 | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8963 mL | 14.4814 mL | 28.9628 mL |
| 5 mM | 0.5793 mL | 2.8963 mL | 5.7926 mL |
| 10 mM | 0.2896 mL | 1.4481 mL | 2.8963 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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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。
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A new nonhydrolyzable reactive cAMP analog, (Sp)-adenosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate irreversibly inactivates human platelet cGMP-inhibited cAMP phosphodiesterase
Bioorg Chem 2002 Feb;30(1):16-31.PMID:11955000DOI:10.1006/bioo.2001.1226.
Levels of cAMP that control critical platelet functions are regulated by cGMP-inhibited cAMP phosphodiesterase (PDE3A). We previously showed that millimolar concentrations of the hydrolyzable 8-[(4-bromo-2,3-dioxobutyl)thioadenosine 3',5'-cyclic monophosphate (8-BDB-TcAMP) inactivate PDE3A. We have now synthesized a nonhydrolyzable affinity label to probe the active site of PDE3A. The nonhydrolyzable adenosine 3',5'-cyclic monophosphorothioates, Sp-cAMPS and Rp-cAMPS, function as competitive inhibitors of PDE3A with K(i) = 47.6 and 4400 microM, respectively. We therefore coupled Sp-cAMPS with 1,4-dibromobutanedione to yield (Sp)-adenosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate, [Sp-cAMPS-(BDB)]. Sp-cAMPS-(BDB) inactivates PDE3A in a time-dependent, irreversible reaction with k(max) = 0.0116 min(-1) and K(I) = 10.1 microM. The order of effectiveness of protectants in decreasing the rate of inactivation (with K(d) in microM) is: Sp-cAMPS (24) > Rp-cGMPS (1360), Sp-cGMPS (1460) > GMP (4250), AMP (10600), Rp-cAMPS (22170). These results suggest that the inactivation of PDE3A by Sp-cAMPS-(BDB) is a consequence of reaction at the overlap of the cAMP and cGMP binding regions in the active site.
Modulation of cyclic AMP action in the dog thyroid by its agonist and antagonist Sp- and Rp-adenosine 3',5'-monophosphorothioate
Biochem J 1986 Feb 15;234(1):193-7.PMID:3010952DOI:10.1042/bj2340193.
The diastereoisomeric forms of adenosine 3',5'-monophosphorothioate, Sp-cAMPS and Rp-cAMPS, have been shown to mimic and to inhibit activation of protein kinase type I and type II by cyclic AMP. In the present work, Sp-cAMPS mimicked thyrotropin (TSH) action on thyroid hormone secretion and protein iodination in dog thyroid slices, whereas Rp-cAMPS antagonized those effects. The phosphorothioates have been tested as inhibitors or activators of the three major phosphodiesterases: the Ca2+/calmodulin-sensitive form, the cyclic GMP-stimulated form and the cyclic AMP-specific enzyme. At 100 microM Sp-cAMPS inhibited the three enzyme activities. In contrast, Rp-cAMPS failed to stimulate activity of the three enzymes. From a comparison of the biological properties of Sp- and Rp-cAMPS and 3-isobutyl-1-methyl xanthine, it is suggested that one site of action of the phosphorothioates is on the cyclic AMP-dependent protein kinases, i.e. the effects of Sp-cAMPS and Rp-cAMPS observed in intact cell can be ascribed to the agonistic and antagonistic effects on the cyclic AMP-dependent protein kinases. However, partial inhibition of phosphodiesterase activities by the phosphorothioates cannot be excluded.
cAMP-dependent protein kinase and reward-related learning: intra-accumbens Rp-cAMPS blocks amphetamine-produced place conditioning in rats
Psychopharmacology (Berl) 2003 Oct;170(1):23-32.PMID:12768275DOI:10.1007/s00213-003-1510-2.
Rationale: Dopamine may produce reward-related learning by activating D(1)-like receptors in the nucleus accumbens (NAc) and stimulating the formation of cyclic adenosine monophosphate (cAMP) and the activation of cAMP-dependent protein kinase (PKA). Objectives: This hypothesis was tested using the conditioned place preference (CPP) based on NAc injections of amphetamine (amph) and evaluating the effects of PKA inhibition with Rp-cAMPS. Methods: The CPP procedure consisted of three phases: pre-exposure (three 15-min sessions in a chamber consisting of two distinct compartments connected by a tunnel), conditioning (four 30-min placements into one compartment with the tunnel blocked following drug injection into the NAc alternating with four similar placements into the other side following NAc injection of saline), and test (one 15-min session with the tunnel open). A CPP was defined as an increase in time spent on the drug-paired side from mean pre-exposure to test. Results: Dose-response experiments showed that 15.0 or 20.0 but not 5.0 or 10.0 micro g/0.5 micro l per side of amph produced a CPP. The amph (20.0 micro g) CPP was blocked by Rp-cAMPS co-injections of 25.0 and 250 but not 2.5 ng/0.5 micro l per side. Rp-cAMPS or the PKA activator Sp-cAMPS (50.0, 250, 500, 600 ng/0.5 micro l per side) alone had no effect on side preference. Co-injection of 10.0 micro g amph+Sp-cAMPS (25.0, 50.0, 250, 500 ng) did not result in a CPP but co-injection of 20.0 micro g amph+Sp-cAMPS (250 ng) led to a loss of the CPP normally seen with that dose of amph. Doses of Rp-cAMPS that blocked CPP did not block the locomotor stimulatory effect of amph during conditioning sessions. Conclusions: Results supported the hypothesis that PKA activation in NAc is necessary for reward-related learning.
Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways
Invest Ophthalmol Vis Sci 1995 Mar;36(3):730-6.PMID:7890503doi
Purpose: The authors studied the involvement of cAMP-dependent second messenger systems in the inhibition of rod outer segment (ROS) phagocytosis by isoproterenol (ISO) and forskolin (FSK) using two membrane-permeant analogs of cyclic adenosine monophosphate (cAMP), the Rp and Sp diastereoisomers of cyclic adenosine 3',5' monophosphothioate (cAMPS). Rp-cAMPS is a potent competitive inhibitor of cAMP-dependent protein kinase I and II (PKA I and II), whereas Sp-cAMPS is a potent activator of these enzymes. Methods: ROS phagocytosis was quantitated in cultured rat RPE cells using a previously described double immunofluorescence assay. Results: Sp-cAMPS showed a dose-dependent inhibition of ROS phagocytosis, whereas 100 microM Rp-cAMPS had no effect on this process. Rp-cAMPS fully prevented the inhibitory effect of Sp-cAMPS and FSK but was able to prevent only partially the inhibition of ROS phagocytosis induced by ISO. Isoproterenol plus FSK showed an additive effect on the inhibition of phagocytosis, suggesting that they act at two independent sites. However, ISO plus Sp-cAMPS or FSK plus Sp-cAMPS showed no additivity. Conclusions: Results suggest that FSK inhibits ROS phagocytosis by RPE cells through a cAMP-dependent pathway, whereas ISO inhibits ROS phagocytosis by RPE cells through cAMP-dependent and cAMP-independent pathways.
Fear memory consolidation in sleep requires protein kinase A
Learn Mem 2018 Apr 16;25(5):241-246.PMID:29661836DOI:10.1101/lm.046458.117.
It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPS in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory.