Formation and metabolism of inositol 1,4,5 trisphosphate in human platelets

[3H]Myo-inositol (1,4,5)trisphosphate ((1,4,5)IP3), when added to lysed platelets, was rapidly converted to [3H]inositol (1,3,4,5)tetrakisphosphate which was in turn converted to [3H]inositol (1,3,4)trisphosphate. This result demonstrates that platelets have the same metabolic pathways for interconversion of inositol polyphosphates that are found in other cells. Labelling of platelets with [32P]orthophosphate, followed by h.1.p.c. was used to measure thrombin-induced changes in the three inositol polyphosphates. Interfering compounds were removed by a combination of enzymatic and nonenzymatic techniques. [32P]-(1,4,5)IP3 was formed rapidly and reached its maximal level at about 4 sec. It was also rapidly degraded and was no longer detectable after 30-60 sec. Formation of (1,3,4,5)IP4 was almost as rapid as that of (1,4,5)IP3 and remained at detectable levels for a longer time. (1,3,4)IP3 was formed after an initial lag and this isomer reached its maximal level that was ten-fold higher than that of (1,4,5)IP3 at 30 sec. Comparison of the intracellular Ca2+ concentration as measured with fura-2 indicates that agents other than (1,4,5)IP3 are responsible for the sustained maintenance of a high level of intracellular Ca2+. It is proposed that either (1,3,4)IP3 or (1,3,4,5)IP4 may also be Ca2+-mobilizing agents