Summary
Ticlopidine, when orally administered to rats, resulted in activation of basal and
prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase
in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of
the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity
caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced
by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine
3’,5’-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate
was not significantly affected by Ticlopidine treatment.
These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin
synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.
