Disease relevance of Dinoprostone

• Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02) [1].
• Nocistatin blocks nociceptin-induced allodynia and hyperalgesia, and attenuates pain evoked by prostaglandin E2 [2].
• Here we provide evidence that prostaglandin E2 (PGE2) rapidly phosphorylates EGFR and triggers the extracellular signal-regulated kinase 2 (ERK2)--mitogenic signaling pathway in normal gastric epithelial (RGM1) and colon cancer (Caco-2, LoVo and HT-29) cell lines [3].
• Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy [3].
• Vaginal prostaglandin E2 and fatal amniotic fluid embolus [4].

Psychiatry related information on Dinoprostone

• Prostaglandin E2: a neuromodulator in the central control of gastrointestinal motility and feeding behavior by calcitonin [5].
• A repeated measures model was used to assess the effect of BMI and physical activity as predictors of PGE2 concentration [6].
• Prostaglandin E2 enhances gastric defense mechanisms against acid injury in uremic rats [7].
• Prostaglandin E2 (600 fmol/min) had no effect on increasing the amounts of both slow wave sleep and paradoxical sleep [8].
• These results indicate that PGE2 modifies cataplexy through a central effect and suggest that this prostaglandin may play a role in rapid-eye-movement sleep regulation [9].

High impact information on Dinoprostone

• Ca2+ oscillations in astrocytic endfeet can control cerebral microcirculation through the arachidonic acid metabolites prostaglandin E2 and epoxyeicosatrienoic acids that induce arteriole dilation, and 20-HETE that induces arteriole constriction [10].
• In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section [11].
• Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type [12].
• Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus, but it is less costly, is easier to administer, and is associated with fewer adverse effects [13].
• A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second-trimester pregnancy [13].

Chemical compound and disease context of Dinoprostone

• Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients [14].
• Similarly, hearts challenged with fMLP 30 d following infarction released only small amounts of the cyclooxygenase products (thromboxane, 42 +/- 8 ng/5 min; prostacyclin, 386 +/- 31 ng/5 min; PGE2, 79 +/- 25 ng/5 min) [15].
• These data indicated that hyperglycemia is inhibiting Na+,K(+)-ATPase activity by the sequential activation of PKC and cPLA2, resulting in the liberation of arachidonic acid and increased the production of PGE2, which are known inhibitors of Na+,K(+)-ATPase [16].
• Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production [17].
• While pretreatment of CCDs with pertussis toxin blocked PGE2 inhibition of vasopressin-stimulated water permeability, it did not block the effect of PGE2 on JNa [18].

Biological context of Dinoprostone

• PGE2, a chief cyclooxygenase product, modulates blood pressure and fertility, although the specific G protein-coupled receptors mediating these effects remain poorly defined [19].
• Inactivation of EGFR kinase with selective inhibitors significantly reduces PGE2-induced ERK2 activation, c-fos mRNA expression and cell proliferation [3].
• Since it has been observed that IL-2 inhibits the catalytic activity of adenylate cyclase and that agents such as PGE2 which stimulate adenylate cyclase activity inhibit the lymphoproliferative response to IL-2, association of GTP binding proteins with IL-2 signal transduction was investigated [20].
• In chromaffin cells, two different second messenger pathways are activated by PGE2 binding to an apparently single EP3 receptor class [21].
• As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2, and is a major source of PGE2, we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways [22].

Anatomical context of Dinoprostone

• Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus [23].
• Thus, human leukocytic pyrogen can act on skeletal muscle to stimulate intralysosomal proteolysis by increasing the production of prostaglandin E2 [24].
• We show that the vitronectin receptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E2/TGF-beta release and ornithine decarboxylase activity in macrophages [25].
• Role of PGE2 in anion exchange in gastric mucosa [26].
• In human neutrophils, the sum of the lipoxygenase products 5-HETE, 11-HETE and 5,12-di-HETE substantially exceeds the total amount of PGE2 and other cyclo-oxygenase metabolites that are generated concurrently, and the endogenous lipoxygenase products regulate neutrophil function [27].

Associations of Dinoprostone with other chemical compounds

• The formation of prostaglandin E2 increased during supplementation with safflower oil and tended to decrease with fish oil; no prostaglandin E3 metabolite was detected [28].
• Biosynthesis of prostacyclin in rat liver endothelial cells and its control by prostaglandin E2 [29].
• Somatostatin, a tetradecapeptide with potent inhibitory actions on gastric acid secretion, potentiated carbamylcholine-induced synthesis and release of prostaglandin E2 from isolated perfused rat stomachs [30].
• PGD2 and PGE2 accumulated in the culture medium at the stages of trophozoites and schizonts more actively than at the ring stage [31].
• When PGE1 and PGE2 (0.1 microM) were added exogenously to the enriched lymphocyte population, OAF release occurred after stimulation with PHA [32].

Gene context of Dinoprostone

• To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-) [19].
• Native human IL-1 beta and IL-1 alpha stimulated prostaglandin E2 secretion by human embryonic lung fibroblasts at half-maximal concentrations of 3 +/- 1.2 pM (+/- SEM) and 10 +/- 2.3 pM, respectively [33].
• Comparison of the biological response curves and binding curves obtained for IL-1 alpha and IL-1 beta showed that they were parallel and that 10-15% occupancy of the estimated 3,000 sites by either species of IL-1 was sufficient to give half-maximal stimulation of prostaglandin E2 secretion [33].
• 3LL tumor cells constitutively express cyclooxygenase (COX)-1 and COX-2 and produce high levels of PGE2 [34].
• In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production [35].

Analytical, diagnostic and therapeutic context of Dinoprostone

• The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostaglandin E2 (dinoprostone [PGE2]) [13].
• The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed [11].
• Urinary prostaglandin E2 levels were diminished but returned to normal after discontinuation of drug therapy and recovery of renal function [36].
• We showed the presence of prostaglandin E2 (PGE2) by bioassay and radioimmunoassay [37].
• Kinetic studies were conducted on cell-free extracts derived from cells cultivated for 1 d, using [1-14C]arachidonic acid as substrate and measuring the label in PGE2 after extraction and thin layer chromatography [38].

References