BM-520, an original TXA(2) modulator, inhibits the action of thromboxane A(2) and 8-iso-prostaglandin F-2 alpha in vitro and in vivo on human and rodent platelets, and aortic vascular smooth muscles from rodents
[en] Thromboxane A(2) (TXA(2)) and 8-iso-PGF(2 alpha). are two prostanoid agonists of the thromboxane A(2) receptor (TP), whose activation has been involved in platelet aggregation and atherosclerosis. Agents able to counteract the actions of these agonists are of great interest in the treatment and prevention of cardiovascular events. Here, we investigated in vitro and in vivo the pharmacological profile of BM-520, a new TP antagonist. In our experiments, this compound showed a great binding affinity for human washed platelets TP receptors, and prevented human platelet activation and aggregation induced by U-46619, arachidonic acid and 8-iso-PGF(2 alpha). The TP receptor antagonist property of BM-520 was confirmed by its relaxing effect on rat aorta smooth muscle preparations precontracted with U-46619 and 8-iso-PGF(2 alpha). Further, its TP antagonism was also demonstrated in vivo in guinea pig after a single intravenous injection (10 mg kg(-1)). We conclude that this novel TP antagonist could be a promising therapeutic tool in pathologies such as atherosclerosis where an increased production of TXA(2) and 8-iso-PGF2., as well as TP activation are well-established pathogenic events. (c) 2007 Elsevier Inc. All rights reserved.
Cherdon, Céline ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie générale, bioch. et path. humaine et pathologiques
Pratico, Domenico
Masereel, Bernard
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
✱ These authors have contributed equally to this work.
Language :
English
Title :
BM-520, an original TXA(2) modulator, inhibits the action of thromboxane A(2) and 8-iso-prostaglandin F-2 alpha in vitro and in vivo on human and rodent platelets, and aortic vascular smooth muscles from rodents
Publication date :
2007
Journal title :
Prostaglandins and Other Lipid Mediators
ISSN :
1098-8823
Publisher :
Elsevier Science Inc, New York, United States - New York
Wang L.H., and Kulmacz R.J. Thromboxane synthase: structure and function of protein and gene. Prostaglandins Other Lipid Mediat 68-69 (2002) 409
Hirata M., Hayashi Y., Ushikubi F., et al. Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature 349 (1991) 617
Huang J.S., Ramamurthy S.K., Lin X., and Le Breton G.C. Cell signalling through thromboxane A2 receptors. Cell Signal 16 (2004) 521
Moncada S., and Vane J.R. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev 30 (1978) 293
Gurbel P.A., Murugesan S.R., Lowry D.R., and Serebruany V.L. Plasma thromboxane and prostacyclin are linear related and increased in patients presenting with acute myocardial infarction. Prostaglandins Leukot Essent Fatty Acids 61 (1999) 7
Wenzel S.E. Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacotherapy 17 (1997) 3S
Dogne J.M., de Leval X., Delarge J., David J.L., and Masereel B. New trends in thromboxane and prostacyclin modulators. Curr Med Chem 7 (2000) 609
Dogne J.M., Hanson J., de Leval X., et al. Pharmacological characterization of N-tert-butyl-N′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time. J Pharmacol Exp Ther 309 (2004) 498
Dogne J.M., Hanson J., and Pratico D. Thromboxane, prostacyclin and isoprostanes: therapeutic targets in atherogenesis. Trends Pharmacol Sci 26 (2005) 639
Dogne J.M., Hanson J., de Leval X., et al. From the design to the clinical application of thromboxane modulators. Curr Pharm Des 12 (2006) 903
Morrow J.D., Minton T.A., Mukundan C.R., et al. Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes. J Biol Chem 269 (1994) 4317
Lawson J.A., Rokach J., and FitzGerald G.A. Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J Biol Chem 274 (1999) 24441
Crankshaw D. Effects of the isoprostane, 8-epi-prostaglandin F2 alpha, on the contractility of the human myometrium in vitro. Eur J Pharmacol 285 (1995) 151
Sametz W., Hennerbichler S., Glaser S., Wintersteiger R., and Juan H. Characterization of prostanoid receptors mediating actions of the isoprostanes, 8-iso-PGE2 and 8-iso-PGF2α in some isolated smooth muscle preparations. Br J Pharmacol 130 (2000) 1903
Fukunaga M., Yura T., Grygorczyk R., and Badr K.F. Evidence for the distinct nature of F2-isoprostane receptors from those of thromboxane A2. Am J Physiol 272 (1997) F477
Cracowski J.L., Devillier P., Durand T., Stanke-Labesque F., and Bessard G. Vascular biology of the isoprostanes. J Vase Res 38 (2001) 93
Morrow J.D. The isoprostanes-unique products of arachidonate peroxidation: their role as mediators of oxidant stress. Curr Pharm Des 12 (2006) 895
Pratico D., Iuliano L., Mauriello A., et al. Localization of distinct F2-isoprostanes in human atherosclerotic lesions. J Clin Invest 100 (1997) 2028
Pratico D., Tangirala R.K., Rader D.J., Rokach J., and FitzGerald G.A. Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice. Nat Med 4 (1998) 1189
Mallat Z., Philip I., Lebret M., Chatel D., Maclouf J., and Tedgui A. Elevated levels of 8-iso-prostaglandin F2alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation 97 (1998) 1536
Delanty N., Reilly M.P., Pratico D., et al. 8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo. Circulation 95 (1997) 2492
Antczak A., Montuschi P., Kharitonov S., Gorski P., and Barnes P.J. Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. Am J Respir Crit Care Med 166 (2002) 301
Dworski R., Murray J.J., Roberts L.J., et al. Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress. Am J Respir Crit Care Med 160 (1999) 1947
Davi G., Falco A., and Patrono C. Determinants of F2-isoprostane biosynthesis and inhibition in man. Chem Phys Lipids 128 (2004) 149
Friedel H.A., and Buckley M.M.T. Torasemide. A review of its pharmacological and therapeutic potential. Drugs 41 (1991) 81
Dogne J.M., Wouters J., Rolin S., et al. Design, synthesis and biological evaluation of a sulfonylcyanoguanidine as thromboxane A2 receptor antagonist and thromboxane synthase inhibitor. J Pharm Pharmacol 53 (2001) 669
Nuhrich A., Varache-Lèmbege M., Lacan F., and Devaux G. Use of infrared spectroscopy in monitoring a new method for the preparation of sulotroban, an antithrombotic drug. J Chem Educ 319 (1996) 689
Masereel B., Damas J., Fontaine J., et al. Thromboxane A2 receptor antagonism in man and rat by a sulphonylcyanoguanidine (BM-144) and a sulphonylurea (BM-500). J Pharm Pharmacol 51 (1999) 695
Dogne J.M., de Leval X., Neven P., et al. Effects of a novel non-carboxylic thromboxane A2 receptor antagonist (BM-531) derived from torasemide on platelet function. Prostaglandins Leukot Essent Fatty Acids 62 (2000) 311
Dogne J.M., de Leval X., Kolh P., et al. Pharmacological evaluation of the novel thromboxane modulator BM-567 (I/II). Effects of BM-567 on platelet function. Prostaglandins Leukot Essent Fatty Acids 68 (2003) 49
Born G.V., and Cross M.J. The aggregation of blood platelets. J Physiol 168 (1963) 178
Loi C., Chardigny J.M., Berdeaux O., et al. Effects of three trans isomers of eicosapentaenoic acid on rat platelet aggregation and arachidonic acid metabolism. Thromb Haemost 80 (1998) 656
Pratico D., Smyth E.M., Violi F., and FitzGerald G.A. Local amplification of platelet function by 8-Epi prostaglandin F2alpha is not mediated by thromboxane receptor isoforms. J Biol Chem 271 (1996) 14916
Halushka P.V. Thromboxane A(2) receptors: where have you gone?. Prostaglandins Other Lipid Mediat 60 (2000) 175
Cayatte A.J., Du Y., Oliver-Krasinski J., Lavielle G., Verbeuren T.J., and Cohen R.A. The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis. Arterioscler Thromb Vase Biol 20 (2000) 1724
Balsano F., and Violi F. Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group. Circulation 87 (1993) 1563
Pratico D., Tillmann C., Zhang Z.B., Li H., and FitzGerald G.A. Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice. Proc Natl Acad Sci USA 98 (2001) 3358
Rolin S., Dogne J.M., Michaux C., Delarge J., and Masereel B. Activity of a novel dual thromboxane A(2)receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles. Prostaglandins Leukot Essent Fatty Acids 65 (2001) 67
Rolin S., Petein M., Tchana-Sato V., et al. BM-573, a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, prevents pig myocardial infarction induced by coronary thrombosis. J Pharmacol Exp Ther 306 (2003) 59
Ogletree M.L., and Allen G.T. Interspecies differences in thromboxane receptors: studies with thromboxane receptor antagonists in rat and guinea pig smooth muscles. J Pharmacol Exp Ther 260 (1992) 789
Delaey C., and Van de Voorde J. Heterogeneity of the inhibitory influence of sulfonylureas on prostanoid-induced smooth muscle contraction. Eur J Pharmacol 325 (1997) 41
Kemp B.K., and McPherson G.A. Interspecies differences in thromboxane A2 receptors are distinguished by glibenclamide. Eur J Pharmacol 354 (1998) 173
Kinsella B.T., O'Mahony D.J., and Fitzgerald G.A. The human thromboxane A2 receptor alpha isoform (TP alpha) functionally couples to the G proteins Gq and G11 in vivo and is activated by the isoprostane 8-epi prostaglandin F2 alpha. J Pharmacol Exp Ther 281 (1997) 957
