RAPID AND TRANSIENT THROMBIN STIMULATION OF PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE SYNTHESIS BUT NOT OF PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE INDEPENDENT OF PHOSPHOLIPASE-C ACTIVATION IN PLATELETS

When platelets are stimulated by thrombin they immediately undergo ino sitol lipid hydrolysis via phospholipase C activation. However, subseq uently an increased production of phosphatidylinositol 4,5-bisphosphat e is observed. Phospholipases C were inhibited by lowering the cytopla smic free calcium concentration by preincubation with Quin-2-tetra(ace toxymethyl) ester. Aggregation and secretion were also totally suppres sed. Under these conditions we observed an increased labeling of phosp hatidylinositol 4,5-bisphosphate, indicating a stimulation of inositol lipid kinases, independent of lipid hydrolysis by phospholipase C. Co nversely the production of phosphatidylinositol 3,4-bisphosphate was t otally abolished. These results suggest a different regulation of the kinases/phosphatases responsible for the production of phosphatidylino sitol 4,5-bisphosphate and phosphatidylinositol 3,4-bisphosphate.