The rapid formation of inositol phosphates in human platelets by thrombin is inhibited by prostacyclin.

Abstract The biochemical events underlying the ability of thrombin to enhance the metabolism of inositol phospholipids in human platelets have been investigated using platelets prelabeled with [3H]inositol. Thrombin treatment caused rapid formation of radioactive inositol monophosphate (IP), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) with less marked and more variable changes in the levels of radioactive inositol phospholipids. Formation of IP2 and IP3 could be detected 5 s after exposure to thrombin and before IP levels increased. Low doses of thrombin which produced only shape change in human platelets also caused significant formation of IP2 and IP3 but not IP. These results suggest that thrombin-induced platelet activation may be mediated through hydrolysis of polyphosphoinositides. The majority of IP formed presumably arises from the hydrolysis of IP2. Prostacyclin inhibited thrombin-induced formation of all three inositol phosphates.