Inositol 1,4,5‐trisphosphate (IB3) induced rapid formation of thromboxane B2 in saponin‐permeabilised human platelets: mechanism of IP3 action

Abstract

The mechanism of IP₃‐induced activation of saponin‐permeabilised platelets has been examined. Saponin permeabilisation resulted in the leakage of low‐M _r substances into and from the cells without loss of cytoplasmic proteins. Addition of IP₃ rapidly induced a dose‐related formation of thromboxane B₂ and release into the medium, leading to the responses of shape change, aggregation and [¹⁴C]5HT release. These responses were inhibited by the thromboxane A₂ receptor antagonist AH23848. The IP₃‐induced release of ⁴Ca from intracellular stores was not affected by indomethacin. Synthesis of thromboxane was inhibited if Ca²⁺ elevation was prevented by using Ca‐EGTA buffers during permeabilisation. These studies indicate that IP3‐induced activation was due to Ca²⁺ mobilisation leading to phospholipase activation and thromboxane synthesis.