Enhancement of collagen-induced phosphoinositide turnover by thromboxane A2analogue through Ca2+mobilization in human platelets

Abstract

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.