Disease relevance of carbacyclin

• Moreover, the carbaprostacyclin-induced bone resorption was completely blocked by an antisense phosphothiorate oligodeoxynucleotide of PPARdelta/beta but not by the sense phosphothiorate oligodeoxynucleotide of the same DNA sequence [1].
• Beneficial effects of a new carbacyclin derivative, ZK 36 374, in acute myocardial ischemia [2].
• Paracetamol administered i.p. at 100 mg kg-1 reduced the peritoneal levels of 6-keto-PGF1 alpha and inhibited zymosan-induced but not carbacyclin-induced writhing and did not produce behavioural toxicity [3].
• Prevention by a carbacyclin analogue (ZK 36 374) of digoxin-induced ventricular extrasystoles in guinea-pig myocardium [4].
• The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls [5].

High impact information on carbacyclin

• In addition, the stable PGI(2) analog, carbaprostacyclin, and a synthetic PPARdelta agonist induced transactivation of endogenous PPARdelta in human colon carcinoma cells [6].
• Two inhibitors of cAMP-dependent protein kinase, a specific peptide inhibitor of the catalytic subunit of cAMP protein kinase and KT5720, blocked the inhibitory effect of carbacyclin, indicating that the inhibition of IP3-induced Ca2+-release by carbacyclin is mediated by cAMP-dependent protein kinase [7].
• This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin [8].
• The effects of iloprost, carbaprostacyclin, and treprostinil on the regulation of phagocytosis, bacterial killing, and inflammatory mediator production were determined in both macrophage populations from rats [9].
• Interestingly, treatment with PGI(2) or its stable analog, carbaprostacyclin, augmented IL-10 production by Th2 cells [10].

Chemical compound and disease context of carbacyclin

• The two prostacyclin receptor agonists restored cerebral vasodilation to hypercapnia that had been blocked by indomethacin (to 92 +/- 31% and 76 +/- 11% of the before-indomethacin dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of PGE2 partially restored the dilation (43 +/- 7% of the pre-indomethacin response) [11].
• Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes [12].

Biological context of carbacyclin

• Carbacyclin derivative E/Z-2d was found to be essentially inactive as an inhibitor of ADP induced human platelet aggregation, having an IC50 of >10 micromol/L [13].
• These results emphasize the adipogenic, nonmitogenic role of cPGI2 and also allow the distinction between the various adipogenic/mitogenic factors which affect adipose cell differentiation [14].
• However, treatment of intact platelets with phorbol 12-myristate 13-acetate, thrombin or carbacyclin did not increase PS-p68 phosphorylation [15].
• In contrast, carbaprostacyclin (cPGI2), a stable analogue of prostacyclin, behaves as a true adipogenic factor leading to a 4 to 5-fold increase in GPDH-specific activities with no significant effect on cell growth [14].
• Intra-arterial 9-beta-methyl carbacyclin improved early PTFE graft patency and inhibited platelet deposition in a severe canine model, independent of baseline platelet aggregation status, which also had an important effect on graft patency [16].

Anatomical context of carbacyclin

• Type II-sPLA(2) induction was obtained after treatment of the cells by 15-deoxy-Delta(12,14)-dehydroprostaglandin J(2), carbaprostacyclin, and 9-hydroxyoctadecadienoic acid, which are ligands of peroxisome proliferator-activated receptor (PPAR) gamma, whereas PPARalpha ligands were ineffective [17].
• Confluent fibroblasts were subjected to a differentiation protocol, involving a serum-free defined medium supplemented with insulin, triiodothyronine, carbaprostacyclin, thyrotropin, dexamethasone, and isobutylmethylxanthine [18].
• 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 [19].
• In addition, carbaprostacyclin enhanced both a limited proliferation and terminal differentiation of adipose precursor cells isolated from rodent and human adipose tissues maintained in primary culture [20].
• This binding may be due to the presence of an EP1-receptor, since iloprost and 6a-carba PGI2 but not cicaprost are known to have potent EP1-receptor agonist actions on smooth muscle preparations [21].

Associations of carbacyclin with other chemical compounds

• This binding was displaced with unlabeled prostanoids in the order of cicaprost > iloprost, both prostacyclin agonists > PGE1 > carbacyclin >> PGD2 approximately STA2, a thromboxane A2 agonist approximately PGE2 > PGF2 alpha [22].
• Prostaglandins E2, F2 alpha and D2, unable to affect the cyclic AMP production, failed to substitute for carbaprostacyclin [20].
• Upon removal of EGF from the culture medium, complete resumption of differentiation occurs, whereas upon removal of PGF2 alpha or SMGK, complete resumption only takes place when differentiation is triggered by cPGI2 [14].
• Linoleic acid and carbaprostacyclin, both peroxisome proliferator-activated receptor delta and alpha ligand-activators, were more effective but less specific, stimulating lipid formation in both types of cells [23].
• The order of potency may be similar on horse platelet membranes, but the analysis is complicated by the presence of a second component of [3H]-iloprost binding that is inhibited by iloprost and 6a-carba PGI2 but not by cicaprost [21].

Gene context of carbacyclin

• Macrophages harvested from prostaglandin I (IP) receptor-deficient mice showed the up- and down-regulatory effects on the cytokine production by the EP2 and EP4 agonists or PGE(2), but no effect was obtained by carbacyclin [24].
• Addition of PGE2 (10 microM) and the stable analog of PGI2, carbaprostacyclin (5 microM), to Hep3B cells also increased VEGF expression [25].
• Exogenous PGE2 and carbacyclin (a stable derivative of PGI2) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1 beta-challenged HGF [26].
• Postischemic recovery of LVDP in COX-1(-/-) and COX-2(-/-) was unchanged by perfusion with 5 micromol/L PGE(2), PGD(2), PGF(2alpha), or carboprostacyclin [27].
• Treatment of IP-expressing cells with the stable agonist carbaprostacyclin failed to alter the ratios of oligomeric/dimeric/monomeric forms of the receptor, suggesting that IP dimerization/oligomerization is an agonist-independent process [28].

Analytical, diagnostic and therapeutic context of carbacyclin

• A subcutaneous infusion pump was used to deliver either saline solution (control) or 9-beta-methyl carbacyclin (Ciprostine) at 100 (CARB-100) or 200 ng/kg/min (CARB-200) through a femoral artery branch just proximal to one of the femoral grafts, with the contralateral graft serving as a noninfused control [16].
• A chemically stable prostacyclin analogue (PGI2-A, carbacyclin, OP-41483) was evaluated as an adjunct to potassium cardioplegia in infants (n = 13) and children (n = 32), in whom the current potassium cardioplegia may be limited in its effects [29].
• 2) With oral administration to guinea pigs, OP-41483 given as its alpha-cyclodextrin clathrate (OP-41483 alpha-CD) inhibited platelet adhesiveness at doses higher than 1.0 mg/kg (expressed in terms of OP-41483), whereas PGl2 and carbacyclin did not at 10 mg/kg [30].
• 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 [31].

References