Carbacyclin (Carbaprostacyclin)
(Synonyms: Carbaprostacyclin; Carba-PGI2) 目录号 : GC32487
A stable analog of PGI2
Cas No.:69552-46-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Primary cultures of neonatal rat cardiomyocytes are prepared from the ventricles of 1-day-old Wistar rats, and are seeded at a density of 4 × 105/6-well plastic plates, 9 × 105/60 mm dishes, or 3 × 106/100 mm dishes with Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (FCS). After 40 h of incubation, cultured cardiomyocytes are serum-starved for 8 h before Carbacyclin stimulation. |
Animal experiment: | Mice[3]Ten to twelve week-old male C57BL/6 mice (20-25 g) are used in the experiment. Mice (n = 4) are injected intraperitoneally with 100 μg of Carbacyclin, and are sacrificed at the times indicated. The hearts are excised, and the ventricles are then homogenized with 3 mL of Isogen for the following total RNA extraction procedure[3]. |
References: [1]. Takasuka M, et al. FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2 alpha, prostacyclin receptor agonist (carbacyclin), and their related compounds in dilute CCl4 solution: structure-activity relationships. J Med Chem. 1994 Jan 7;37(1):47-56. | |
Carbaprostacyclin is a stable analog of PGI2. When infused in rabbits or dogs, it inhibits ex vivo platelet aggregation, but the effect persists only 10 minutes after termination of the infusion. This implies rapid metabolic inactivation of carbaprostacyclin.1 Carbaprostacyclin inhibits platelet aggregation with 10% of the molar potency exhibited by PGI2.1,2 The ED50 of carbaprostacyclin for the in vitro inhibition of ADP-
1.Whittle, B.J.R., Moncada, S., Whiting, F., et al.Carbacyclin — a potent stable prostacyclin analogue for the inhibition of platelet aggregationProstaglandins19(4)605-627(1980) 2.Aiken, J.W., and Shebuski, R.J.Comparison in anesthetized dogs of the anti-aggregatory and hemodynamic effects of prostacyclin and a chemically stable prostacyclin analog, 6a-carba-PGI2 (carbacyclin)Prostaglandins19(4)629-643(1980) 3.Adaikan, P.G., Karim, S.M.M., and Lau, L.C.Platelet and other effects of carbaprostacyclin - a stable prostacyclin analogueProstaglandins Med.5(4)307-320(1980) 4.Aubert, J., Ailhaud, G., and Negrel, R.Evidence for a novel regulatory pathway activated by (carba)prostacyclin in preadipose and adipose cellsFEBS Lett.397(1)117-121(1996)
| Cas No. | 69552-46-1 | SDF | |
| 别名 | Carbaprostacyclin; Carba-PGI2 | ||
| Canonical SMILES | O=C(O)CCC/C=C1C[C@@]2([H])C[C@@H](O)[C@H](/C=C/[C@@H](O)CCCCC)[C@@]2([H])C\1 | ||
| 分子式 | C21H34O4 | 分子量 | 350.49 |
| 溶解度 | DMF: >10 mg/ml (from 6B-PGI2),DMSO: >5 mg/ml (from 6B-PGI2),Ethanol: >20 mg/ml (from 6B-PGI2),PBS pH 7.2: >80 µ g/ml (from 6B-PGI2) | 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 | 2.8531 mL | 14.2657 mL | 28.5315 mL |
| 5 mM | 0.5706 mL | 2.8531 mL | 5.7063 mL |
| 10 mM | 0.2853 mL | 1.4266 mL | 2.8531 mL |
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| 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 | ||||||||||
| 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.
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Targeted delivery of Carbaprostacyclin to ischemic hindlimbs enhances adaptive remodeling of the microvascular network
Hypertension 2013 May;61(5):1036-43.PMID:23529172DOI:10.1161/HYPERTENSIONAHA.111.00458.
Prostacyclin and its stable analogs play an important vascular protective role by promoting angiogenesis, but their role in arteriolar growth is unclear. Here, we examined the effect of prostacyclin stable analog Carbaprostacyclin on arteriolar growth in mouse hindlimb ischemia. Using an osmotic-controlled release system to continuously deliver Carbaprostacyclin or saline (control) to ischemic mouse hindlimbs for up to 14 days, we found that blood perfusion was significantly better at 7 and 14 days in carbaprostacyclin-treated mice than in saline-treated mice. Microscopic examination of the microvasculature showed more morphological signs of arteriolar formation in carbaprostacyclin- versus saline-treated legs. A double-blind, quantitative microcomputed tomography analysis indicated that carbaprostacyclin-treated legs had markedly increased vascular volume and small- to medium-sized vessel numbers that correspond to decreased vessel separation. A proteome profiler antibody array demonstrated that carbaprostacyclin-treated ischemic muscles secreted significantly higher amounts of acidic fibroblast growth factor and other chemokines. Conditioned media containing those secreted factors promoted smooth muscle cell growth and migration. Additionally, increased acidic fibroblast growth factor protein levels were detected in smooth muscle cells and skeletal myotubes at different time periods after Carbaprostacyclin treatment. Furthermore, the selective peroxisome proliferation-activated receptor β/δ antagonist significantly suppressed carbaprostacyclin-induced acidic fibroblast growth factor protein production. Collectively, our data provide the first morphological and molecular evidence that local delivery of Carbaprostacyclin promotes vascular growth in hindlimb ischemia, and that peroxisome proliferation-activated receptor β/δ signaling plays a critical role in inducing acidic fibroblast growth factor expression.
Carbacyclin--a potent stable prostacyclin analogue for the inhibition of platelet aggregation
Prostaglandins 1980 Apr;19(4):605-27.PMID:6992234DOI:10.1016/s0090-6980(80)80010-4.
Carbacyclin is a chemically stable analogue of prostacyclin. As an inhibitor of platelet aggregation induced by ADP or collagen in vitro, Carbacyclin is 0.03 times as active as prostacyclin in human, dog or rabbit plasma. Carbacyclin, like prostacyclin, reduces systemic arterial blood pressure (BP) in dogs, rabbits and rats and is not inactivated during passage through the pulmonary circulation. Further actions were investigated using a new ex vivo technique which allows rapid preparation of platelet-rich plasma and determination of platelet aggregation. In the dog, intravenous infusion of Carbacyclin or prostacyclin inhibits platelet aggregation ex vivo with minimal effects on BP or heart rate. In the anaesthetised or conscious rabbit, Carbacyclin and prostacyclin produces similar cardiovascular changes in doses producing an equivalent degree of platelet inhibition. In both rabbit and dog, Carbacyclin is 0.1 times as active as prostacyclin in inhibiting ex vivo platelet aggregation. Platelet inhibition is maintained throughout the period of infusion of either compound (up to 3 h) yet is no longer apparent 10 min after terminating the infusion. Carbacyclin is thus a chemically-stable but metabolically-unstable analogue with a biological profile closely similar to prostacyclin.
Trans-placental transport and metabolism of Carbacyclin by perfused human placental in vitro
Prostaglandins 1989 Jan;37(1):121-34.PMID:2655009DOI:10.1016/0090-6980(89)90036-1.
When Carbacyclin (5E-6a-carba-prostaglandin I2) was added to the maternal afferent circulation of in vitro perfused placentae from normal term pregnancies, relatively little Carbacyclin was found in either the maternal or fetal efferent circulations. When Carbacyclin was added to the perfusate at 1.0 microM, the peak level in the maternal effluent was only 0.06 microM and in the fetal effluent, 0.026 microM. When infused at 10 microM, 0.77 microM Carbacyclin was measured in the maternal effluent and 0.13 in the fetal effluent. These findings demonstrate that Carbacyclin is transferred across the placenta from the maternal side to the fetal, but that the net transfer is small. The assay procedure employed HPLC resolution, followed by capillary gas chromatography and selected ion monitoring using PGB as an internal standard. The low levels of Carbacyclin detected in the effluents did not result from poor recovery in the analyses. When Carbacyclin was added to maternal or fetal effluents at 1 microM, the recovery averaged 85.4 +/- 14.1% (SD); at 10 microM recovery averaged 97.3 +/- 4.2%. Much of the loss of Carbacyclin on passage through placental circulation resulted from metabolism. Extracts of both fetal and maternal effluents from placenta perfused with Carbacyclin contained a component which on reverse phase HPLC appeared less polar than Carbacyclin. When analyzed by GC/MS as the methyl ester-trimethylsilyl ether, this component had a mass spectrum expected for 15-dehydro-carbacyclin. When the presumed metabolite was further converted to the methoxime, the mass spectrum was identical to published spectra for that derivative of 15-dehydro-carbacyclin. When extracts of fetal effluents were analyzed for 15-dehydro-carbacyclin metabolite as well as Carbacyclin, it appeared that the metabolite accounted for the majority of the Carbacyclin recovered. Most of the metabolite was apparently not formed in the fetal circulation, since when Carbacyclin was added to the fetal afferent circulation, little 15-dehydro-carbacyclin was observed in either efferent fluid, and most of the perfused Carbacyclin was recovered unaltered in the fetal effluent.
The prostacyclin analogue Carbacyclin inhibits Ca(2+)-activated K+ current in aortic baroreceptor neurones of rats
J Physiol 1997 Jun 1;501 ( Pt 2)(Pt 2):275-87.PMID:9192300DOI:10.1111/j.1469-7793.1997.275bn.x.
1. Previous studies indicate that prostacyclin (PGI2) increases the activity of baroreceptor afferent fibres. The purpose of this study was to test the hypothesis that PGI2 inhibits Ca(2+)-activated K+ current (IK(Ca))in isolated baroreceptor neurones in culture. 2. Rat aortic baroreceptor neurones in the nodose ganglia were labelled in vivo by applying a fluorescent dye (DiI) to the aortic arch 1-2 weeks before dissociation of the neurones. Outward K+ currents in baroreceptor neurones evoked by depolarizing voltage steps from a holding potential of -40 mV were recorded using the whole-cell patch-clamp technique. 3. Exposure of baroreceptor neurones to the stable PGI2 analogue Carbacyclin significantly inhibited the steady-state K+ current in a dose-dependent and reversible manner. The inhibition of K+ current was not caused indirectly by changes in cytosolic Ca2+ concentration. The Ca(2+)-activated K+ channel blocker charybdotoxin (ChTX, 10(-7) M) also inhibited the K+ current. In the presence of ChTX or in the absence of Ca2+, Carbacyclin failed to inhibit the residual K+ current. Furthermore, in the presence of high concentrations of Carbacyclin, ChTX did not cause further reduction of K+ current. 4. Carbacyclin-induced inhibition of IK(Ca) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTP gamma S. The inhibitory effect of Carbacyclin on IK(Ca) was abolished by GDP beta S, which blocks G-protein activation, and by a selective inhibitor of cAMP-dependent protein kinase, PKI5-24. 5. The results demonstrate that Carbacyclin inhibits ChTX-sensitive IK(Ca) in isolated aortic baroreceptor neurones by a G-protein-coupled activation of cAMP-dependent protein kinase. This mechanism may contribute to the PGI2-induced increase in baroreceptor activity demonstrated previously.
Carbaprostacyclin, a PPARdelta agonist, ameliorates excess lipid accumulation in diabetic rat placentas
Life Sci 2010 May 22;86(21-22):781-90.PMID:20338185DOI:10.1016/j.lfs.2010.03.008.
Aims: Maternal diabetes impairs placental development and metabolism. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors relevant in metabolic homeostasis. We investigated the concentrations of PPARdelta and its endogenous agonist prostacyclin (PGI2), as well as the effects of carbaprostacylin (cPGI(2,) a PPARdelta agonist) on lipid metabolism in placentas from control and streptozotocin-induced diabetic rats on day 13.5 of gestation. Main methods: The placentas were explanted to evaluate PPARdelta expression and PGI2 concentrations, and cultured with cPGI2 for further analysis of lipid metabolism (concentrations and (14)C-acetate derived synthesis of triglycerides, cholesteryl esters, phospholipids, cholesterol and free fatty acids; release of glycerol and lipid peroxidation). Key findings: Reduced PGI2 concentrations were found in the placentas from diabetic rats when compared to controls. cPGI2 additions reduced the concentrations and synthesis of several lipid species, increased lipid catabolism and reduced lipid peroxidation in the placenta. These effects were more marked in diabetic tissues, which presented alterations in the lipid metabolic parameters evaluated. cPGI2 additions increased placental PPARdelta and acyl-CoA oxidase expression, which are changes possibly involved in the catabolic effects observed. Significance: The present study reveals the capability of cPGI2 to regulate placental lipid metabolism and PPARdelta expression, and suggests that preserving appropriate PGI2 concentrations in the placenta may help to metabolize maternal derived lipid overload in diabetic gestations.