sq-29548 and ifetroban

sq-29548 has been researched along with ifetroban* in 3 studies

Other Studies

3 other study(ies) available for sq-29548 and ifetroban

ArticleYear
Intracellular signaling by 8-epi-prostaglandin F2 alpha is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries.
    Biochemical and biophysical research communications, 1996, Aug-23, Volume: 225, Issue:3

    To investigate the mechanisms for intracellular signaling and increased vascular tone by 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha), we measured mitogen-activated protein kinase (MAPK) activity and myosin regulatory light chain (LC20) phosphorylation in porcine carotid arteries incubated with 8-epi-PGF2 alpha or PGF2 alpha. With stimulation by either 8-epi-PGF2 alpha or PGF2 alpha. MAPK activity and the force of contraction rose in parallel and were maintained during the time of exposure to agonist (2 hours). LC20 phosphorylation levels rose and then partially declined during stimulation with either agonist. The effects of 8-epi-PGF2 alpha on contraction, MAPK activity, and myosin light chain phosphorylation were completely inhibited by the receptor antagonists, SQ-29548 and BMS-180291; the effects of PGF2 alpha were only partially inhibited by these compounds. Thus, intracellular signaling by 8-epi-PGF2 alpha in fully differentiated vascular smooth muscle, resulting in MAPK activation and increased myosin phosphorylation, is specifically mediated by an activation of thromboxane A2/prostaglandin endoperoxide receptors. Lipid peroxidation and 8-epi-PGF2 alpha production, resulting from such vascular pathological processes as atherosclerosis, lead to an activation of two intracellular signaling pathways in smooth muscle: one pathway results in the activation of MAPK, while the other results in myosin light chain phosphorylation.

    Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Calcium-Calmodulin-Dependent Protein Kinases; Carotid Arteries; Dinoprost; F2-Isoprostanes; Fatty Acids, Unsaturated; Hydrazines; In Vitro Techniques; Muscle, Smooth, Vascular; Myosin Light Chains; Oxazoles; Phosphorylation; Receptors, Prostaglandin; Receptors, Thromboxane; Signal Transduction; Swine; Vasoconstriction

1996
Pharmacological profile of BMS 180,291: a potent, long-acting, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.
    The Journal of pharmacology and experimental therapeutics, 1993, Volume: 264, Issue:2

    180,291 1S-(1 alpha, 2 alpha, 3 alpha, 4 alpha)-2-[[3-[4- [(pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept- 2- yl]methyl]benzenepropanoic acid (BMS) is a potent and highly selective antagonist of thromboxane A2/prostaglandin endoperoxide (TP) receptors. In human platelet-rich plasma, BMS 180,291 inhibited platelet aggregation induced by arachidonate (800 microM) and U-46,619 (10 microM) with respective IC50 values of 7 +/- 1 (S.E.M.) and 21 +/- 2 nM. Inhibition of both the rate and full extent of 11,9-epoxymethano-prostaglandin H2 (U-46,619)-induced platelet aggregation were insurmountable at antagonist concentrations > 10 nM, but BMS 180,291 antagonized U-46,619-induced platelet shape change competitively with a KB of 11 +/- 2 nM. BMS 180,291 concentrations < or = 1 mM did not inhibit platelet aggregation induced by high concentrations of ADP (20 microM) or human alpha-thrombin (1 U/ml). BMS 180,291 inhibited binding of [3H]1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]-7-[3-[[2- [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]-hept-2- yl]-5-heptenoic acid to human platelet membranes with a kd of 4.0 +/- 1.0 nM and slope factor of 1.06 +/- 0.13. U-46,619-induced concentrations of rat aortae were competitively antagonized by BMS 180,291 with a KB of 0.6 +/- 0.1 nM. Aortic responses to norepinephrine, serotonin and angiotensin II were not inhibited by BMS 180,291 at 1 microM. U-46,619-induced contractions of guinea pig tracheal rings were antagonized in an almost all-or-none manner, with maximal blockade at > or = 1 nM BMS 180,291, but little effect at lower concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Administration, Oral; Animals; Aorta; Bridged Bicyclo Compounds, Heterocyclic; Cattle; Coronary Vessels; Dinoprostone; Fatty Acids, Unsaturated; Guinea Pigs; Humans; Hydrazines; In Vitro Techniques; Male; Mice; Muscle Contraction; Oxazoles; Platelet Aggregation; Propionates; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin; Receptors, Thromboxane; Swine; Thromboxane B2; Trachea

1993
Binding and function of a potent new thromboxane receptor antagonist, BMS 180,291, in human platelets.
    The Journal of pharmacology and experimental therapeutics, 1993, Volume: 264, Issue:3

    Binding and function of BMS 180,291 ([(+)1S-(1 alpha,2 alpha,3 alpha,4 alpha)]-2-[[3-[4-[(n-pentylamino)carbonyl]-2-oxazolyl]-7- oxabicyclo[2.2.1] hept-2-yl]methyl]benzenepropanoic acid]) in human platelets was examined. Kinetic determination of [3H]BMS 180,291 binding produced ligand-receptor association and dissociation rates of 1.4 x 10(7) +/- 0.2 M-1 x min-1 (n = 5) and 0.04 +/- 0.005 min-1 (n = 5), respectively. The resultant Kd was 3.1 +/- 1.1 nM (n = 5). Saturation binding analysis in platelet membranes was consistent with a single class of [3H]BMS 180,291 binding sites with a Kd of 3.6 +/- 0.19 nM (n = 4) and a binding site maxima (Bmax) of 2099.1 +/- 70.3 fmol/mg of protein (n = 4). Specific [3H]BMS 180,291 binding was inhibited by thromboxane A2/endoperoxide receptor antagonists and agonists with a rank order of potency of: BMS 180,291 > or = SQ 29,548 = I-BOP race 15-(1 alpha,2 beta(5Z), 3 alpha(1E,3S),4 alpha) d7-[3-(3-hydroxy-4-(p-iodophenoxy)-1-butenyl)-7- oxabicyclo[2.2.1]hept-2-yl]5-heptenoic acid) > or = BM 13,505 > or = SQ 30,741 = U 44,609 > U 46,619 >> BM 13,177. Prostaglandin E2 and prostacyclin did not appreciably inhibit the specific binding of [3H]BMS 180,291. BMS 180,291 (10 nM-5 microM) shifted the I-BOP-induced platelet shape change curve to the right in a parallel manner without reduction of the maximal response (KB = 13 +/- 3.5 nM; pA2 = 8 +/- 0.2; slope = -1.0 +/- 0.05), whereas 30 nM drug decreased the maximal I-BOP-induced platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Biphenyl Compounds; Blood Platelets; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Fatty Acids, Unsaturated; Heptanoic Acids; Humans; Hydrazines; In Vitro Techniques; Kinetics; Oxazoles; Platelet Aggregation; Propionates; Receptors, Thromboxane

1993