Disease relevance of Tbxa2r

• These findings suggest that TxA2 may be an important mediator in the development of NTN, and that TxA2 receptor antagonist may be useful for the reduction of glomerular injury in this type of nephritis [1].
• Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats [2].
• In the same model, a low dose aspirin and a specific thromboxane A2 receptor antagonist failed to influence proteinuria, glomerulosclerosis, and hypertension, thus excluding a role for either platelet or renal thromboxane A2 in renal disease progression [3].
• Evaluation of the combination of a tissue-type plasminogen activator, SUN9216, and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model [4].
• Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats [5].

High impact information on Tbxa2r

• These data, coupled with observations that activated peripheral T cells can circulate through the thymus, provide evidence that TxA2/TxA2 receptor interaction in the thymic microenvironment, leading to anergy/programmed cell death of activated T cells, may play an important role in the development of acquired unresponsiveness in vivo [6].
• Here we identify a single amino acid substitution (Arg60-->Leu) in the first cytoplasmic loop of the TXA2 receptor in a dominantly inherited bleeding disorder characterized by defective platelet response to TXA2 [7].
• Therefore, 8-epi-PGF2 alpha is a potent preglomerular vasoconstrictor acting principally through TxA2 receptor activation [8].
• Infusion of a TXA2 receptor antagonist into the suprarenal aorta of CSD rats caused a rapid return to normal of RBF (renal blood flow), GFR (glomerular filtration rate), SNGFR, QA, RA, PGC, and Kf (ultrafiltration coefficient) [9].
• Specific thromboxane A2 receptor antagonists, KT1-32 and GR 32191B, did not show any improvement in colonic transit after trinitrobenzene sulfonic acid administration [10].

Chemical compound and disease context of Tbxa2r

• Prevention of thromboxane A2 receptor-mediated pulmonary hypertension by a nonpeptide angiotensin II type 1 receptor antagonist [11].
• 7. The additive antithrombotic effect of the combination of thrombin inhibitor and TXA2 receptor antagonist at low doses suggests that thrombin and TXA2 may work in concert to produce thrombosis [12].
• A clearly sensitizing influence of hyperthyroidism was found for the vasoconstrictor effects of both 5-HT (6.57 +/- 0.04 vs. 6.29 +/- 0.06; hyperthyroid vs. control) and the thromboxane A2 receptor agonist U46619 (6.78 +/- 0.13 vs. 6.30 +/- 0.09; hyperthyroid vs. control) [13].
• Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548 [14].
• The effect of TNF-alpha (100 ng/mL) on pulmonary Kf was compared with that of lungs exposed to LPS (400 microg/mL; E. coli 0111:B4) or a TxA2 receptor agonist (U-46619; 7 x 10(-8)) [15].

Biological context of Tbxa2r

• Assignment of the gene for rat thromboxane receptor (Tbxa2r) to chromosome 7q11 by fluorescence in situ hybridization [16].
• This observation, together with the increased maximal vasoconstriction to the thromboxane A2 receptor agonist U46619 after 2 weeks of bosentan administration, suggests that bosentan also interacts with the receptors mediating endothelium-dependent contractions [17].
• Following KCl stimulation and TXA2 receptor blockade, ONOO- induced NO-dependent muscle relaxation in newborn vessels via stimulation of the endothelial and inducible nitric oxide synthases [18].
• Human bronchial smooth muscle cell proliferation via thromboxane A2 receptor [19].
• TXA2 receptor blockade prevented PGF2 alpha- and PGE2-induced aortic contraction and cell myosin light chain phosphorylation, but not cell signaling or protein synthesis [20].

Anatomical context of Tbxa2r

• cDNA cloning of a thromboxane A2 receptor from rat astrocytes [21].
• Recently, we cloned a cDNA for rat kidney thromboxane receptor (Tbxa2r) and showed that Tbxa2r is expressed in the renal glomerulus, vasculature, and transitional cell epithelium of renal pelvis [16].
• The presence of the thromboxane A2 receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined [22].
• In in vitro studies, cultured vascular smooth muscle cells incubated with uric acid also generated COX-2 with time-dependent proliferation, which was prevented by either a COX-2 or TXA-2 receptor inhibitor [23].
• These observations indicate that in mesangial cell immune injury the protective effect of thromboxane A2 receptor antagonism on glomerular filtration rate and renal blood flow is not solely due to inhibition of the vasoconstrictor effects of thromboxane A2 [24].

Associations of Tbxa2r with chemical compounds

• 3. Bosentan preincubation produced a significant parallel rightward shift of the contractions to U46619, a selective thromboxane A2 receptor agonist [25].
• Both TXA2 synthase inhibitor furegrelate (Fureg) and TXA2 receptor antagonist SQ-29548 (SQ) substantially blocked enhanced increase of PP in the LPS group (4.9 +/- 0.4 vs. 3.6 +/- 0.5 vs. 2.6 +/- 0.6 mmHg for LPS alone, LPS + Fureg, and LPS + SQ, respectively; P < 0.05) while having no significant effect on controls [26].
• Contraction stimulated by endothelin-1, noradrenaline, KCl, or the TXA2 receptor agonist U-46619 were unaffected by BMS-180560 (1 nM) [27].
• These results indicate that cinnamophilin is a selective thromboxane A2 receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel blocking properties [28].
• Surprisingly, SQ29548, 1 microM, a selective PGH2 /thromboxane A2 receptor blocker, also reduced angiotensin II responses (62 +/- 4%; p < 0.05) [29].

Regulatory relationships of Tbxa2r

• This stimulation is specifically mediated by TxA2 (thromboxane prostanoid, TP) receptors, since U-46619 also stimulates PAI-1 expression in cells that are transfected with TP receptors, and this stimulation of PAI-1 production is completely blocked by the TxA2 receptor antagonist, SQ-29,548 [30].

Other interactions of Tbxa2r

• Effects of ANG II, ETA, and TxA2 receptor antagonists on cyclosporin A renal vasoconstriction [31].
• Preadministration of both a cyclooxygenase inhibitor and a thromboxane A2 receptor antagonist attenuated the degree of endotoxin-induced liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)[22]
• In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-beta mRNA levels [32].
• 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) [33].
• We also postulated that TNF-alpha potentiates the effect of interleukin-1beta (IL-1beta) or TxA2 receptor activation on pulmonary microvascular permeability [15].

Analytical, diagnostic and therapeutic context of Tbxa2r

• Administration of the TxA2 receptor blocker prior to transplantation or 2 wk postengraftment completely abrogated the unresponsive state [6].
• Perfusion of hearts with serotonin receptor antagonist LY53,857 (10(-6) M), thromboxane A2 receptor antagonist SQ29,548 (10(-6) M), adenine nucleotide scavenger apyrase (0.4 units/ml), or nitric oxide synthetase inhibitor NG-monomethyl-L-arginine (2 x 10(-4) M) attenuated (p < 0.05) the platelet-mediated cardioprotective effects [34].
• This study was designed to investigate the possible involvement of the thromboxane A2 (TXA2)-TXA2 receptor (TXA2R) system of the hepatic sinusoid in cold preservation/reperfusion injury in liver grafts [35].
• FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor antagonist S-145 and related compounds. 3. Conformation and activity of S-145 analogues [36].
• These results indicate that thromboxane A2 is an important mediator of skeletal muscle reperfusion injury and suggest that administration of a thromboxane A2 receptor antagonist may improve limb salvage rates after surgery for acute ischaemia [37].

References