The effects of ticlopidine (Ti) on arachidonic acid (AA) metabolism in platelet phospholipids have been studied in vitro by following AA release from (14C) AA-prelabeled platelets or by measuring (14C)-AA incorporation into platelet phospholipids.In the presence of prelabeled platelets, Ti induced a release of AA essentially from phosphatidylcholine (PC) only at concentrations (10-3 M) where the drug became lytic. Incubation of cells previously lysed by sonication led to a deacylation of PC, part of the released AA being reincorporated into phosphatidylethanolamine (PE) . Under these conditions, Ti effect on PC disappeared and only a slight inhibition of AA incorporation into PE was observed.On the other hand, upon incubation of non-labeled platelets with (14C)-AA, Ti impaired the incorporation of AA into all platelet phospholipids, half maximum effect being observed under non-lytic conditions at 10-5-5.10-5 M.It is postulated that Ti inhibits the acylation reactions responsible for AA entry into glycerophospholipids. This effect might promote the release of trace amounts of AA in intact cells, which could explain the accumulation of stable, anti-aggregating prostaglandin D2 (M. Lagarde et al. Prostagl. Med. 1979, 2, 433).
