BIOMAT Database Logo BIOMAT Database Logo

Effects of free and macromolecular-bound TXA2 receptor antagonist BM 13.505 on U46619-induced platelet aggregation. 1993

J L Klimm, and M A Kloczewiak, and J Lindon
Department of Anesthesia, Massachusetts General Hospital, Boston.

The goal of this study was to synthesize a macromolecular probe of the TXA2 receptor antagonist BM13.505 which is unable to penetrate the platelet membrane for localization and characterization of the TXA2 receptor. The active NHS-ester of BM13.505 was synthesized and purified. It was used for covalent coupling of BM13.505 to bovine serum albumin, a macromolecular carrier. Inhibitory effects of free and macromolecular bound BM13.505 on aggregatory properties of U46619-stimulated platelets were measured and compared to TXA2 generation in platelets, as determined by TXB2 radioimmunoassay. No inhibitory effects of free and macromolecular-bound BM13.505 on ADP- or thrombin-induced platelet aggregation were observed. Equimolar concentrations of free or macromolecular bound BM13.505 inhibited U46619-induced platelet aggregation and TXA2 generation with equal potency. IC50-values for platelet aggregation inhibition by free and macromolecular bound BM13.505 were 64 nM and 96 nM respectively. It appears that the TXA2 receptor ligand binding site is located close to the outer membrane surface of platelets. Interaction of macromolecular bound BM13.505 with the platelet thromboxane receptor does not depend on the availability of the free carboxyl residue in BM13.505. The method for coupling a TXA2 receptor antagonist to a macromolecule will aid in constructing probes for the localization and characterization of the TXA2 receptor.

UI MeSH Term Description Entries
D010648 Phenylacetates Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID. Benzeneacetates,Benzeneacetic Acids,Phenylacetic Acids,Acids, Benzeneacetic,Acids, Phenylacetic
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D011450 Prostaglandin Endoperoxides, Synthetic Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds. Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000244 Adenosine Diphosphate Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. ADP,Adenosine Pyrophosphate,Magnesium ADP,MgADP,Adenosine 5'-Pyrophosphate,5'-Pyrophosphate, Adenosine,ADP, Magnesium,Adenosine 5' Pyrophosphate,Diphosphate, Adenosine,Pyrophosphate, Adenosine
D012710 Serum Albumin, Bovine Serum albumin from cows, commonly used in in vitro biological studies. (From Stedman, 25th ed) Fetal Bovine Serum,Fetal Calf Serum,Albumin Bovine,Bovine Albumin,Bovine Serum Albumin,Albumin, Bovine,Albumin, Bovine Serum,Bovine Serum, Fetal,Bovine, Albumin,Calf Serum, Fetal,Serum, Fetal Bovine,Serum, Fetal Calf
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin

Related Publications

J L Klimm, and M A Kloczewiak, and J Lindon
Beneficial effects of a thromboxane receptor antagonist (BM 13.505) on platelet hyperreactivity and thromboxane formation in cholesterol-fed rabbits.
January 1988, Biomedica biochimica acta,
J L Klimm, and M A Kloczewiak, and J Lindon
Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation induced by U46619, a TXA2 analogue.
December 2006, The Journal of pharmacy and pharmacology,
J L Klimm, and M A Kloczewiak, and J Lindon
Antagonism of U46619-induced aggregation of human and canine platelets by four TXA2 receptor antagonists.
November 1986, Thrombosis research,
J L Klimm, and M A Kloczewiak, and J Lindon
Inhibitory effects of the selective thromboxane receptor antagonist BM 13.177 on platelet aggregation, vasoconstriction and sudden death.
January 1984, Biomedica biochimica acta,
J L Klimm, and M A Kloczewiak, and J Lindon
Effects of platelet activating factor antagonists on arachidonic acid-induced platelet aggregation and TXA2 formation.
November 1990, Prostaglandins, leukotrienes, and essential fatty acids,
J L Klimm, and M A Kloczewiak, and J Lindon
Protective effects of the thromboxane receptor antagonists BM 13.177 and BM 13.505 against U 46619-induced sudden death in rats.
January 1988, Pharmacology,
J L Klimm, and M A Kloczewiak, and J Lindon
Effect of the thromboxane receptor antagonist, BM 13.505, on the sequelae of endotoxemia in the conscious rat.
January 1988, Eicosanoids,
J L Klimm, and M A Kloczewiak, and J Lindon
Local anesthetic effects on TXA2 receptor mediated platelet aggregation using quenched flow aggregometry.
January 1999, Advances in experimental medicine and biology,
J L Klimm, and M A Kloczewiak, and J Lindon
BM 13.505, a selective thromboxane receptor antagonist, reduces myocardial infarct size following coronary artery reperfusion.
October 1989, Prostaglandins, leukotrienes, and essential fatty acids,
J L Klimm, and M A Kloczewiak, and J Lindon
Mutations of the platelet thromboxane A2 (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity.
November 1999, Thrombosis and haemostasis,
Copied contents to your clipboard!