Disease relevance of SQ 28053

• TxB2 and 6-keto-PGF1 alpha, measured in blood samples obtained from the coronary artery distal to the thrombus, were significantly increased at reperfusion and at reocclusion in control animals and in dogs receiving SQ 29548 [1].
• Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets [2].
• The recovery of force generation of IMA, but not RA, upon reoxygenation after 30 min of hypoxia was significantly reduced in the initial phase of reoxygenation by indomethacin and SQ-29548 and by endothelin receptor blocker BQ-123 [cyclo(l-Leu-d-Trp-d-Asp-l-Pro-d-Val)] [3].
• GBS-induced pulmonary hypertension could be reversed by SQ 29548; SRI 63072 did not affect PPA when administered to pigs with GBS-induced elevation in PPA [4].
• The response was receptor specific since arrhythmias were absent after pretreatment with a specific TxA(2) receptor antagonist (SQ-29548) and did not occur in response to another prostaglandin, PGF(2alpha) [5].

High impact information on SQ 28053

• The administration of the thromboxane receptor antagonist SQ 29548 in IL-2-treated rats led to a reversal of the fall in GFR induced by the lymphokine without significant changes in urinary sodium excretion [6].
• Treatment with a thromboxane A2 receptor blocker, SQ 29548, decreased blood pressure in Ang II-salt hypertensive rats from 191 +/- 9 to 152 +/- 9 mm Hg after 3 hours, but it had no effect on blood pressure in normotensive rats [7].
• SQ-29548, a TP receptor antagonist, diminished the db/db mice vascular smooth muscle contractile hyperreactivity [8].
• In control arterioles, exogenous H(2)O(2) (0.1-100 mumol/l) elicited dilations (maximum, 58 +/- 10%), whereas in arterioles of db/db mice H(2)O(2) caused constrictions (-28 +/- 8%), which were converted to dilations (maximum, 16 +/- 5%) by the thromboxane A(2)/prostaglandin H(2) (TP) receptor antagonist SQ-29548 [9].
• Insulin treatment normalized both the glucose levels and the vasodilatory responses, and SQ-29548 treatment had no effect on functional or AA-mediated vasodilation in STZ + insulin animals [10].

Chemical compound and disease context of SQ 28053

• Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 microM SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs [11].
• Furegrelate or SQ-29548 partially inhibited the pressor effect and bradycardia elicited by melittin [12].

Biological context of SQ 28053

• The TP-receptor antagonist SQ-29548 inhibited only U-46619+epinephrine-induced GPIIb/IIIa activation, P-selectin expression, and platelet aggregation [13].
• 2. Superfusion of I-BOP (0.5 microM) resulted in a biphasic change of the excitatory postsynaptic potential (e.p.s.p.), which was blocked by pretreatment with SQ 29548, a specific antagonist of TXA2 receptors [14].
• Stimulation with I-BOP induced apoptosis in a dose-dependent manner and was completely prevented by a TxA(2) receptor antagonist, SQ-29548 [15].
• The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548 [16].
• The specific role of TxA2 was investigated by pretreatment with OKY-046, a specific Tx synthase inhibitor, or infusion of SQ 29548, a TxA2 receptor antagonist; both compounds failed to protect against either the PMA-induced permeability or the vascular resistance increase [17].

Anatomical context of SQ 28053

• Specific displacement of [3H]SQ 29548 was demonstrated in COS-7 cell membranes with the unlabeled TP receptor antagonist SQ 29548 (Kd = 12.6+/-1.1 nM) and the TP receptor agonist U46619 (Kd = 192.1+/-58.9 nM), but not with other prostaglandins (PGD2, PGE1, PGF2alpha), or the PGI2 mimetic cicaprost [18].
• Protective actions of a thromboxane receptor antagonist, SQ 29548 on the ischemic myocardium: morphologic and hemodynamic effects [19].
• SQ 29548 did not alter the Phe actions in CT4 aortas [20].
• Competitive inhibition of specific binding of the TxA2 analogue [125I]BOP by unlabeled antagonists in intact cells or membranes was observed, with a rank order potency of SQ-29548 (half-maximal inhibitory concentration = 3.4 nM > L-657925 (21 nM) > GR-32191 (200 nM) > L-657926 (1,300 nM) [21].
• In aortic rings with endothelium contracted with phenylephrine, a subthreshold concentration of PGH2, but not U 46619, impaired relaxations to acetylcholine; the inhibition was prevented by treatment with SQ 29548 or superoxide dismutase, indicating that the abnormality of endothelial cell function was specific for PGH2 [22].

Associations of SQ 28053 with other chemical compounds

• Indomethacin and SQ 29548 had identical actions, preventing the decrease of GFR and antinatriuresis evoked by hyperchloremia, e.g., sodium excretion rate in the SQ 29548 and indomethacin groups increased to 7.2 +/- 1.3 and 7.1 +/- 1.2 microEq/min, respectively, compared with 2.6 +/- 0.7 microEq/min in the control group [23].
• In contrast to control tissue, indomethacin (10 microm), the COX-2 inhibitor NS 398 (10 microm), the TXA2/PGH2 receptor antagonist SQ 29548 (1 microm) and the TXA2 synthase inhibitor furegrelate (1 microm) reduced 5-HT contraction of LPS-treated arteries from hour one [24].
• 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 [25].
• Dazoxiben (a pure TX synthase inhibitor) and SQ 29548 (a pure TXA2 receptor antagonist) did not affect cyclic AMP levels in AA-treated platelets.(ABSTRACT TRUNCATED AT 250 WORDS)[26]
• We found that the IL-1-induced increase in contraction in response to ANG II was completely inhibited by 10(-5) M of the cyclooxygenase inhibitor indomethacin and also by 10(-5) M of the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 [27].

Gene context of SQ 28053

• Indomethacin, the prostaglandin H2/thromboxane A2 receptor antagonist SQ 29548 (0.3 microM), and the nonselective endothelin-1 (ET-1) receptor antagonist bosentan (3 microM) all abolished insulin potentiation of the NA response in obese MAB [28].
• The thromboxane A2 receptor antagonist, SQ 29548, reduced by 53% the calcium signal evoked by 1 microM Tg, which became similar to that induced by 15 microM tBuBHQ [29].
• The thromboxane A2-prostaglandin H2 receptor blocker (1 mumol/L SQ 29548) had no effect on the arteries from either group [30].
• The thromboxane A2 receptor antagonist, SQ 29548, and the 5-lipoxygenase inhibitor, caffeic acid, were without significant effect [31].
• In separate protocols, microperfused OMDVR were pretreated with U63577A or SQ-29548, after which they were exposed to luminal Ang II to induce vasoconstriction [32].

Analytical, diagnostic and therapeutic context of SQ 28053

• The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments [33].
• The stable TX mimetic U-46619 caused a dose-dependent increase in perfusion pressure that was inhibited by the TX receptor antagonist SQ 29548 [34].
• In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069 [33].

References