Enhancement of collagen-induced phosphoinositide turnover by thromboxane A₂ analogue through Ca²⁺ mobilization in human platelets

In human washed platelets, collagen-induced phosphoinositide turnover was inhibited by indomethacin, an inhibitor of thromboxane A₂ (TXA₂) formation, particularly at lower doses of collagen. This inhibition was counteracted by the addition of 9,11-epithio-11,12-methano-TXA₂ (STA₂), a stable analogue of TXA₂ as well as by the Ca²⁺ ionophore A23187. STA₂ and A23187 did not stimulate phosphoinositide turnover markedly, but significantly increased cytoplasmic free Ca²⁺ concentrations. The actions of STA₂ were blocked by 13-azaprostanoic acid, a TXA₂ receptor antagonist. These results suggest that TXA₂ is generated during the action of collagen and increases cytoplasmic free Ca²⁺ which then stimulates phosphoinositide turnover in cooperation with collagen.