The effect of ticlopidine on the aggregation of rat blood platelets and on the formation of metabolites from arachidonic acid and 8,11,14-eicosatrienoic acid in rat platelets during aggregation, and in the rat kidney. 1982

J E Vincent, and F J Zijlstra, and M A vd Veerdonk, and I L Bonta

The effect of ticlopidine after oral administration was determined on the aggregation of rat blood platelets and on the formation of cyclo-oxygenase, and lipoxygenase metabolites from arachidonic acid (AA) and 8,11,14-eicosatrienoic acid in rat platelets and in the kidney. 1. Platelet aggregation is inhibited by ticlopidine. The effect is dependent on the dose administered and the amount of collagen used to induce the aggregation. 2. After the incubation of platelets with [1-(14)C]AA and aggregation by collagen, the following substances are formed: thromboxane B2 (TxB2), 12L-hydroxy-5,8, 10-heptodecatrienoic acid (HHT), 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) small amounts of PGE2 and PGD2 and an unknown metabolite. Ticlopidine administration during 3 days leads to an increase in the amounts of TxB2, PGE2, HHT and the unknown metabolite and a decrease in that of AA dependent on the dose administered. After 30 mg/kg the amount of HETE is decreased. 3. Under the same conditions, TxB1, PGE1, 12L-hydroxy-8,10-heptadecadienoic acid (HHD) and HETE (trienoic) are formed from [1-(14)C]8,11,14-eicosatrienoic acid. After 300 mg/kg ticlopidine the amounts of TxB1, PGE1 and HHD are increased. 4. In the rat kidney, [1-(14)C]AA is transformed into PGF 2 alpha, TxB2, PGE2, PGD2, PGA2, HHT and HETE. After ticlopidine administration, PGF 2 alpha, PGE2, PGD2 and PGA2 are increased, depending on the dose administered. 5. In this tissue, PGF 1 alpha, TxB1, PGD1, PGA1, HHD, HETE (trienoic) and an unknown metabolite are formed from [1-(14)C]eicosatrienoic acid. There is no effect from the administration of ticlopidine on the formation of these substances. 6. These results indicate that ticlopidine increases the synthesis of PGs and related substances in rat platelets and the kidney. This effect is due to an enhanced metabolism of AA.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
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
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D005231 Fatty Acids, Unsaturated FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds. Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001095 Arachidonic Acids Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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