N,N,N-TRIMETHYLSPHINGOSINE MODIFIES AGGREGATORY RESPONSE AND ATP RELEASE FROM PLATELETS IN WHOLE-BLOOD

We investigated the influence of N,N,N-trimethylsphingosine (TMS), a p otent inhibitor of protein kinase C (PKC), on whole blood aggregation and ATP release from platelets. The preincubation with TMS at 1 mu M f or 2 min enhanced ATP release during arachidonic acid-induced aggregat ion. The ristocetin-induced agglutination was inhibited in a TMS conce ntration-dependent manner, which suggests that TMS may interact with t he vWF receptor on platelets. TMS suppressed aggregatory response and ATP release from platelets after the addition of collagen. In contrast , the platelet aggregation induced by ADP and 12-O-tetradecanoylphorbo l-13-acetate (TPA) was only slightly inhibited and the ATP release was not influenced after preincubation with TMS. Our results are in contr ast to previous reported data, which were obtained using PRP and washe d platelets.