EFFECT OF THE PAF-RECEPTOR ANTAGONIST SM-12502 ON HUMAN PLATELETS

We analyzed the effect of the PAF receptor antagonist +)-cis-3,5-dimet hyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) on human p latelet aggregation as well as mediator release. After incubation of h uman platelet with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, with hum an thrombin, or with an activator of heterotrimeric G-proteins, sodium fluoride (NaF, in the presence of Al3+). Preincubation of platelets w ith the PAF receptor antagonist led to an inhibition of 12-lipoxygenas e derived 12(S)-HETE and cyclooxygenase derived 12(S)-HHT. Pretreatmen t of platelets with the PAF receptor antagonist SM-12502 prior to acti vation with the Ca ionophore A23187 or PAF also inhibited platelet agg regation.Our data clearly indicate an inhibitory effect of the new PAF receptor antagonist SM-12502 on the formation of platelet derived inf lammatory mediators of the lipoxygenase pathway as well as of the cycl ooxygenase pathway, and furtherone, treatment with the PAF receptor an tagonist diminished platelet aggregation after subsequent specific and unspecific activation.