Disease relevance of Tbxas1

• The combination of a TXA2 receptor antagonist with a thromboxane A synthase inhibitor deserves further study as a potential treatment for acute cerebral infarction [1].
• The administration of OKY-046, a selective TXA-synthase inhibitor in glycerol-treated rats (GTR), significantly prevented the decrease in Ccr (indicating a partial protection against the development of acute renal failure) (ARF) and the increase in urinary TXA2 excretion, while it did not significantly alter urinary prostaglandin (PG) excretion [2].

High impact information on Tbxas1

• We have studied the transcription regulation of the rat thromboxane synthase (TXS) gene by peroxisome proliferator-activated receptor gamma (PPARgamma) in macrophages [3].
• The transcription activity of a cloned 5'-flanking region (1.6 kilobases) of the rat TXS gene (5'FL-TXS) was examined by luciferase reporter gene assay [3].
• TXS mRNA expression and the transcription activity of 5'FL-TXS were inhibited by PPARgamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)), and the thiazolidinedione troglitazone (TRO) in a dose-dependent manner [3].
• In contrast, immunoreactivity for TXS was present in all stages of spermatogenic cells; spermatogonia, spermatocytes, spermatids, and spermatozoa [4].
• RESULTS: Exogenously applied PGH2 or U-46619 caused concentration-dependent contractions of aortic rings, these contractions being blocked by the newly developed, potent and selective PGH2- and TXA2-receptor antagonist BMS-180291, but not by inhibition of TXA synthase or cyclo-oxygenase (using dazoxiben and indomethacin, respectively) [5].

Biological context of Tbxas1

• 3. ZD1542 also inhibited collagen-stimulated TXS in human, rat and dog whole blood giving IC50 values of 0.018, 0.009 and 0.049 microM respectively [6].
• Assignment of rat thromboxane synthase gene (Tbxas) to chromosome 4q21-->q22 by fluorescence in situ hybridization [7].
• RESULTS: Cyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate [8].

Anatomical context of Tbxas1

• We isolated a cDNA for rat thromboxane synthase from the kidney and here show the location of rat thromboxane synthase gene (Tbxas) on rat chromosome 4q21-->q22 by fluorescence in situ hybridization to metaphase chromatin of rat lymphocytes [7].
• We administered a TXA2 receptor antagonist, SQ29,548, and a thromboxane A synthase inhibitor, 1-benzylimidazole (1-BI), to rats subjected to 30 min of reversible forebrain ischaemia [1].

Associations of Tbxas1 with chemical compounds

• 1. The thromboxane A2 synthase (TXS) inhibitory activity and the thromboxane A2 (TP)-receptor blocking action of ZD1542 (4(Z)-6-[2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]-4-(3- pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in vitro on platelets and whole blood from a range of species including man [6].
• In contrast, the thromboxane A synthase inhibitor, dazoxiben, only partially improved abnormal acetylcholine-induced relaxations in aorta from SHR [9].

References