Disease relevance of prostaglandin h2

• The maximal velocity of aggregation (slope) correlated with platelet TXA2/PGH2 receptor number (r = 0.67, p less than 0.001) and was significantly higher (p less than 0.02) in the acute myocardial infarction patients compared with the other study groups [1].
• B16 malignant melanoma cell lines transform arachidonic acid and its transient metabolite, prostaglandin endoperoxide H2, into prostaglandin D2 [2].
• The cancellation of TXA2- and/or of PGH2-mediated pressor mechanisms, after treatment with thromboxane synthase inhibitors or TXA2/PGH2 receptor blockers, lowers blood pressure in rats with angiotensin-dependent hypertension [3].
• Calcium supplementation suppresses 2 degrees HPT, increases t1/2 [3H]25OHD3 and may protect against PGX osteoporosis and osteomalacia [4].
• The PGH2/TXA2 receptors are linked via a pertussis and cholera toxin-insensitive G-protein which has not been fully characterized, but is thought to belong to the Gq class of G-proteins [5].

High impact information on prostaglandin h2

• Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation [6].
• PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vessels [6].
• The paradoxical coronary dilation produced by the arachidonate or the PGH2 suggest that little if any coronary isomerase which converts endoperoxide into PGE2 exists, or that a novel, potent, PG-like substance is produced by the isolated coronary arteries [7].
• Thus, TXA2- dog platelets have impaired PI-PLC activation in response to TXA2/PGH2 receptor agonists secondary to G protein dysfunction, presumably involving a member of the Gq class [8].
• When ND rats were infused with the same combination of the TxA2/PGH2 receptor antagonist and acetylcholine, renal vasodilatation was also significantly greater than with acetylcholine alone [9].

Chemical compound and disease context of prostaglandin h2

• The ability of platelets to synthesize thromboxane B2 (TxB2) from arachidonic acid (AA) or prostaglandin H2 (PGH2) was studied in 26 control subjects, 40 patients with essential hypertension, 20 patients with cerebrovascular disease (CVD) not taking aspirin and 11 patients with CVD taking aspirin [10].
• Because 13-APA does not interfere with arachidonic acid metabolism, the ability of 13-APA to suppress thrombus formation is presumably due to direct antagonism of TXA2/PGH2 at the platelet receptor level [11].
• The present study evaluated the direct involvement of thromboxane A2/prostaglandin H2 (TXA2/PGH2) in the process of thrombus formation at a site of vascular damage [11].
• Platelet endoperoxide/thromboxane A2 (PGH2/TXA2) receptors in patients with myeloproliferative disorders [12].
• On the contrary, ridogrel (inhibitor of tromboxane-synthase and blocker of PGH2 and TxA2 receptors) did not suppress the hypersensitivity to 5-HT [13].

Biological context of prostaglandin h2

• [125I]BOP was competitively displaced from its platelet binding site by stable TXA2/PGH2 analogues [14].
• Ii is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP [15].
• One potential site at which dexamethasone can influence prostanoid-mediated vasoconstriction may be at the level of the vascular TXA2/PGH2 receptor [16].
• Prostacyclin (PG1(2)), PGE2, PGD2, TXA2/PGH2, and sulfidopeptide-LT receptors are being characterized in terms of distribution, signal-transduction mechanisms, and agonist-mediated regulation [17].
• Platelet activation by PGH2/TxA2 is a tightly regulated process, involving both homologous desensitization of at least two receptor subtypes and sensitization of the platelet adenylase cyclase system [18].

Anatomical context of prostaglandin h2

• Adding prostaglandin H2 (PGH2) directly to lymphocytes led to 6KPGF1 alpha production [19].
• The binding of [125I][1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R)4 alpha)]-7-[3-(3- hydroxy-4-(p-iodophenoxy)-1-butenyl)-7-oxabicyclo[2.2.1] heptan-2-yl]-5-heptanoic acid ([125I]BOP), a potent TXA2/PGH2 receptor agonist, to rabbit aortic membranes was saturable, displaceable, and dependent on protein concentration [16].
• Furthermore, vascular smooth muscle cells with functional TXA2/PGH2 receptors were cultured from human saphenous veins and provide a potentially useful in vitro system for the further study of TXA2/PGH2 receptor-mediated phenomena in human vascular tissue [20].
• Identification of functional PGH2/TxA2 receptors on human endothelial cells [21].
• The present study was designed to examine the activation of MAP kinase and S6 kinase in guinea pig coronary artery smooth muscle cells (CASMC) in response to stimulation by a TXA2/PGH2 mimetic, I-BOP ([1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid) [22].

Associations of prostaglandin h2 with other chemical compounds

• This inhibition is reversed by the product of cyclooxygenase activity, 15-hydroxy - 9 alpha,11 alpha - peroxidoprosta - 5,13 - dienoic acid (PGH2), or by the PGH2 analogue and agonist, U-46619 [23].
• TXA2 receptor antagonists block the activity of both TXA2 and PGH2 on platelets and the vessel wall [24].
• Incubation of arachidonic acid or prostaglandin G2 with washed platelets led to formation of an unstable factor that induced irreversible platelet aggregation and caused release of [14C]serotonin from platelets that had been incubated with [14C]serotonin [25].
• In the presence of azo analog I, human platelet aggregation induced by either the prostaglandin endoperoxide PGH2 or arachidonic acid was antagonized [26].
• A prostaglandin F (PGF) synthase was recently purified from bovine lung that catalyzed the reduction of both PGH2 and PGD2 but at different active sites on the enzyme [27].

Gene context of prostaglandin h2

• The formation of prostaglandins requires the catalytic activity of cyclooxygenase (COX) which converts arachidonic acid to the prostaglandin endoperoxide PGH2, from which all other prostaglandins are formed [28].
• Aspirin completely inhibited bis-oxygenation of arachidonate by PGH synthase-1; in contrast, aspirin-treated PGH synthase-2 metabolized arachidonate primarily to 15-hydroxyeicosatetraenoic acid (15-HETE) instead of PGH2 [29].
• Arachidonic acid and nonsteroidal anti-inflammatory drugs induce conformational changes in the human prostaglandin endoperoxide H2 synthase-2 (cyclooxygenase-2) [30].
• Incubations of cells carried out with PGH2 demonstrated that PGE2 synthase activity was increased after a TNFalpha pretreatment [31].
• Aspirin irreversibly inhibits PGHS-1, preventing this isozyme from forming PGH2 or any other oxygenated product; in contrast, aspirin treatment of PGHS-2 causes this enzyme to form 15-hydroxy-5c,8c,11c,13t-eicosatetraenoic acid (15-HETE) instead of PGH2 [32].

Analytical, diagnostic and therapeutic context of prostaglandin h2

• In SHR but not WKY aortas, acetylcholine (10(-5) mol/L, 5 minutes) caused a significant endothelium-dependent release of PGH2 as measured by gas chromatography/mass spectrometry [33].
• Independent identification of brain TXA2/PGH2 receptors was provided by P2Ab/TxAb immunohistochemistry, which demonstrated specific labeling of discrete myelin-containing fiber tracts [34].
• Identification of this protein as the TXA2/PGH2 receptor was based on: 1) an identical electrophoretic mobility to authentic receptor; 2) immunoblotting of TxAb against P1Ab and P2Ab-purified protein; 3) immunoblotting of P1Ab/P2Ab against TxAb-purified protein; and 4) specific [3H]SQ29,548 binding to TxAb-purified protein [34].
• Site-directed mutagenesis of the catalytic tetrad residues revealed that a dyad of Lys77 and His110, and a triad of Tyr52, Lys77, and His110 are essential for the reduction of PGH2 and 9,10-PQ, respectively [35].
• Thus, in SH rats the enhanced arteriolar constriction to increases in intravascular pressure seems to be due to the production of endothelium-derived constrictor factors PGH2 and endothelin [36].

References