Disease relevance of TBXAS1

• A series of N-(heterocyclic alkyl)pyrido[2,1-b]quinazoline-8-carboxamides were evaluated for their ability to antagonize slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea and to inhibit thromboxane synthase in vitro [1].
• Effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism [2].
• Pretreatment with indomethacin, a prostaglandin H synthase inhibitor, or sodium(E)-3[4-(1-imidazolyl-methyl)phenyl]-2-propenoic acid a thromboxane synthase inhibitor, reduced GBS-induced pulmonary hypertension and edema [3].
• BM-573, a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, prevents pig myocardial infarction induced by coronary thrombosis [4].
• Our objective was to determine whether a combined thromboxane synthase inhibitor-receptor antagonist, terbogrel, prevents pulmonary hypertension and the development of aberrant pulmonary arterial responses in newborn piglets exposed to 3 days of hypoxia [5].

High impact information on TBXAS1

• Unexpectedly, L-NAME converted the endothelium-dependent vasodilator action of ADP to an endothelium-dependent vasoconstrictor response that was blocked individually by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor dazoxiben, and the thromboxane A2 receptor antagonist SQ29548 [6].
• Administration of fMLP to the HNK also resulted in a renal vasoconstriction that was partially inhibited by FPL-55712 and that was completely inhibited by the thromboxane synthase inhibitor OKY-1581 [7].
• The fact that gastrointestinal tract is enriched with thromboxane synthase suggests that thromboxane may have significant physiological roles to be recognized in these organs [8].
• Thromboxane synthase has been purified 620-fold from porcine lung microsomes by a three-step purification procedure including Lubrol-PX solubilization, reactive blue-agarose chromatography, and immunoaffinity chromatography [9].
• Two hybridoma cell lines secreting antibodies against thromboxane synthase of porcine lung were produced [8].

Chemical compound and disease context of TBXAS1

• Indomethacin (a cyclooxygenase inhibitor), dazoxiben (a thromboxane synthase inhibitor), or hirudin (a thrombin antagonist) inhibited the thrombin-induced pulmonary vasoconstriction, as well as the pulmonary edema [10].
• Because of the suggested role of the gut in the pathogenesis of septic shock and multiple organ failure, we investigated the effects of the novel dual thromboxane synthase inhibitor and receptor antagonist DTTX-30 (TRASI) on intestinal tissue perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxemia [11].
• Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting [12].

Biological context of TBXAS1

• The open reading frame encodes a 534-amino acid (aa) protein (M(r) 60,451) which shares more than 75% identity with TS from other species and is 30% homologous to several enzymes of the cytochrome P-450 III family [13].
• Both antibodies (when bound to rabbit anti-mouse IgG-Staphylococcus aureus complex) can immunoprecipitate thromboxane synthase from crude enzyme preparations in an active form suggesting that binding was not directed at the active site [8].
• Effect of thromboxane synthase inhibitor, CS-518, on propranolol-induced bronchoconstriction in guinea pigs [14].

Anatomical context of TBXAS1

• TS activity was detectable in the microsomes of Sf9 cells 12-h post-infection and reached maximum by 48 h [13].
• The concentration of immunoreactive thromboxane synthase in porcine tissues as determined by this assay followed the order of platelet greater than colon greater than duodenum greater than lung greater than kidney greater than stomach [8].
• Under basal conditions, H2O2 induced indomethacin-sensitive contractions, which were larger in preparations without than in those with epithelium; the difference was abolished by inhibitors of thromboxane synthase or thromboxane A2 receptors [15].
• Effects of CS-518, a thromboxane synthase inhibitor, on eosinophil function [16].
• In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors [17].

Associations of TBXAS1 with chemical compounds

• Sequence comparison among porcine (p), human (h), and murine (m) TS indicated conservation of eight Cys residues and one putative N-glycosylation site [13].
• Thromboxane synthase was irreversibly inactivated by 15-hydroxy-9 alpha, 11 alpha-peroxidoprosta-5,13-dienoic acid during catalysis and by treatment of 15-hydroperoxyeicosatetraenoic acid [9].
• The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2 content or reductions in arterial PO2 caused by i.v. infusions of arachidonic acid [18].
• Endothelial nitric oxide synthase (eNOS), cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and thromboxane synthase amounts were unaltered in all lung tissue homogenates [19].
• Antagonists of prostaglandins (SC 19220) or leukotrienes (FPL 55712) also diminished the inherent tone, whereas an inhibitor of thromboxane synthase (OKY 046) had no significant effect [20].

Analytical, diagnostic and therapeutic context of TBXAS1

• Monoclonal antibodies to thromboxane synthase from porcine lung. Production and application to development of a tandem immunoradiometric assay [8].

References