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Effect of ticlopidine on arachidonic acid metabolism in platelet phospholipids in vitro

1981; Elsevier BV; Volume: 30; Issue: 12 Linguagem: Inglês

10.1016/0006-2952(81)90368-3

1873-2968

Hugues Chap, Marie‐Françoise Simon, Louis Douste‐Blazy,

Cholesterol and Lipid Metabolism

In the presence of human platelets prelabelled with [14C]arachidonic acid (AA), ticlopidine (10−4–10−3 M) induces a release of radioactive AA essentially from phosphatidylcholine. This effect is more limited with [3H]-8,11,14-eicosatrienoic acid. Phospholipid hydrolysis occurs immediately after addition of the drug, is dose-dependent and is accompanied by cell lysis. If platelets are previously lysed by sonication, further incubation at 37° leads to a deacylation of phosphatidylcholine, part of the released AA being reincorporated into phosphatidylethanolamine. Under these conditions, ticlopidine effect on phosphatidylcholine disappears and only a slight inhibition of AA incorporation into phosphatidylethanolamine is observed. On the other hand, upon incubation of non-labelled platelets with [14C]-AA, ticlopidine impairs the incorporation of AA into all platelet phospholipids under conditions which are no longer lytic for the cells. Half maximum effect is observed at 10−5 M and 5.10−5 M for phosphatidylcholine and phosphatidylinositol, respectively. It is thus concluded that ticlopidine inhibits the acylation reactions responsible for AA entry into glycerophospholipids. This effect is insufficient for inducing extensive phospholipid hydrolysis unless cell lysis is obtained. However, it might be responsible for the release of trace amounts of AA in intact cells. These results are discussed in relation to the recent finding that ticlopidine promotes an increased synthesis by platelets of prostaglandins D2 and E1 (M. Lagarde et al., Prostagl. Med.2, 433–449, 1979), which might be involved in the antiaggregating effect of the drug.