Disease relevance of SQ29548

• Endothelial migration and corneal angiogenesis are similarly inhibited by a TXA2 receptor antagonist, SQ29548 [1].
• The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin [2].
• Lipoxygenase inhibition (10 microM AA861) alone or in combination with thromboxane receptor antagonism (10 microM SQ29548) had no effect on PAF-induced weight gain [3].
• 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 [4].
• The competition curve for STA2 inhibition of [3H]SQ29548 binding was shifted to the right and was steeper in the presence of GTP gamma S. Pertussis toxin (IAP) elicited ADP-ribosylation of 41KD protein but had no effect on the sensitivity to GTP of the STA2 inhibition of SQ29548 binding or of STA2-induced accumulation of IPs [5].

High impact information on SQ29548

• Hypoxia-reoxygenation selectively blunted prostacyclin (PGI2)-dependent vasorelaxation and elicited a sustained vasoconstriction that was blocked by a cyclooxygenase inhibitor, indomethacin, and SQ29548, a thromboxane (Tx)A2/prostaglandin H2 receptor antagonist, but not by CGS13080, a TxA2 synthase blocker [6].
• The membrane from COS-7 cells transiently transfected with rTXR2 cDNA was shown to be specifically bound by a thromboxane receptor antagonist, SQ29548 [7].
• Topical application of exogenous PGF2 alpha and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agonist was shifted to the right by the increasing concentrations of SQ29548 (10(-6)-10(-8) M) [8].
• Furthermore, the thromboxane A2 receptor antagonist, SQ29548, did not block EGF's vasoconstrictive effects [9].
• Furthermore, SQ29548, a thromboxane/prostaglandin (PG) H(2) (TP) receptor antagonist, significantly reduced the increased endothelial cell apoptosis and the expression of soluble intercellular adhesion molecule-1 that occurred in cells exposed to high glucose, without affecting the decrease in PGIS activity [10].

Chemical compound and disease context of SQ29548

• In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity [2].

Biological context of SQ29548

• Tyrosine phosphorylation of p27 and p31 in response to collagen, but not thrombin, is prevented by aspirin and the TXA(2) receptor antagonist SQ29548, indicating that the effect of collagen strongly relies on TXA(2) signaling [11].
• In this experimental setting, the administration of SQ29548 reduced preglomerular vascular resistance selectively [12].
• SQ29548, a thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation but not TXB(2) production [13].
• The supernatant did not affect the Kd or Bmax of [125I]PTA-OH or the IC50 of the TXA2/PGH2 antagonist, SQ29548 [14].
• 2 The four rabbit aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the thromboxane receptor antagonist SQ29548 [15].

Anatomical context of SQ29548

• The contractile response was partially dependent on the presence of endothelium and was abolished by pretreatment of the rings with either indomethacin or the endoperoxide/thromboxane receptor antagonist, SQ29548 [16].
• 6. Concentration-dependent constriction to 8-epi PGF2 alpha in porcine coronary arteries was inhibited in a concentration-dependent manner by SQ29548 (10(-8) M to 10(-7) M) and BM13505 (10(-8) M to 10(-6) M) [17].
• 3. The ability of U46619 to abolish EDHF-evoked smooth muscle hyperpolarization was prevented by prior exposure of mesenteric arteries to the TXA(2) receptor antagonist 1 microm SQ29548 [18].
• 8-epi-PGF2 alpha induced concentration-dependent contractions in pulmonary arteries (EC50: 7.7 +/- 2.1 microM; n = 3) and aortas (EC50: 0.9 +/- 0.1 microM; n = 4) which were blocked by the TXA2 receptor antagonists SQ29548, L657925 and L657926 [19].
• Mesenteric arteries exhibited attenuation of ACh-stimulated relaxations during repetitive precontraction/relaxation cycles that was not prevented by SQ29548 [20].

Associations of SQ29548 with other chemical compounds

• Since the cyclooxygenase inhibitor indomethacin and the endoperoxide/thromboxane antagonist SQ29548 block epinephrine- and ADP-induced inositol phosphate production, it can be concluded that these agonists activate phospholipase C secondary to mobilization of arachidonic acid and production of cyclooxygenase products [21].
• In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080 [22].
• Prostaglandin F2 alpha induced a concentration-dependent contraction of the rat aorta that was nearly abolished by the thromboxane A2 receptor antagonist, SQ29548 [23].
• Strips were submaximally contracted with noradrenaline and concentration-response curves (CRCs) to acetylcholine (ACh) were constructed before and after treatment with 5 micromol/L atropine, 20 micromol of the cyclooxygenase inhibitor indomethacin and 10 micromol of the PGH2/thromboxane A2 receptor antagonist SQ29548 [24].
• Saralasin further attenuated endothelin-1 response by 65 +/- 2% (p < 0.05), whereas SQ29548 was without effect [25].

Gene context of SQ29548

• Preincubation of HUVECs with SQ29548, a TXA2 receptor antagonist, dose-dependently inhibited platelet-induced COX-2 expression and prostanoid synthesis [26].
• However, in contrast to that which occurred in ULTR cells, SQ29548 abolished 8-epiPGF(2alpha) mediated ERK and JNK activation through both TPalpha and TPbeta in HEK 293 cells providing further evidence that 8-epiPGF(2alpha) may signal through alternative receptors, in addition to the TPs, in human uterine ULTR cells [27].
• The presence of the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80+/-4%) [28].
• Furthermore, preincubation of whole blood with 75 micro mol L-1 or 150 micromol L(-1) SQ29548, a TxA2 receptor antagonist, completely blocked epinephrine's promoting effect on LPS-induced IL-8 release [29].
• Furthermore, SQ29548, a thromboxane A2/prostaglandin H2 receptor antagonist, significantly reduced CD40L-enhanced expression of intercellular adhesion molecule-1 [30].

Analytical, diagnostic and therapeutic context of SQ29548

• This constriction was attenuated (16 +/- 3%) in the presence of 10(-8) M SQ29548 and abolished with 10(-6) or 10(-4) M SQ29548 [8].
• Before reperfusion of group 2 hearts, support rats received either vehicle (group 2a, n = 6) or thromboxane A2 receptor antagonist SQ29548 (0.2 mg/kg) (group 2b, n = 5) [31].

References