IN-VITRO EFFECT OF D-MYO-INOSITOL 1,2,6-TRISPHOSPHATE (PP-56) ON AGGREGATION OF PLATELETS FROM NORMAL AND DIABETIC RATS - RELATIONSHIP TO MALONDIALDEHYDE RELEASE AND PHOSPHOINOSITIDE PATHWAY

In the present study, we investigated the in vitro effects of D-myo-in ositol 1,2,6-trisphosphate (PP-56) on platelets from normal and strept ozotocin-induced diabetic rats. PP-56 markedly inhibited aggregation, in a dose-related manner, when added in vitro, more efficiently with t hrombin- than with ADP-induced aggregation and, after 90 min incubatio n, more in diabetic than in normal platelets. The PP-56 platelet inhib itory effect seems to be related to its phosphate content. PP-56 block ed the release of malondialdehyde from erythrocytes, but to the same e xtent in normal and diabetic rats. PP-56, after 20 min incubation, res tored the platelet phosphoinositide turnover, which was significantly modified in diabetic rats. This last observation could explain at leas t part of the specificity of PP-56 for normalizing platelet aggregatio n in diabetic animals after long-term administration in vivo.