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.
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.
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000494:pharmacology*; D013988:Ticlopidine
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D013876:Thiophenes; D016718:Arachidonic Acid; D003094:Collagen; D015126:8,11,14-Eicosatrienoic Acid; D013988:Ticlopidine