Calcium-dependent stimulation of platelet aggregation by PGE₂

Abstract

THERE is considerable interest in the effects of prostaglandins on blood platelets, partly because the synthesis of prostaglandins by stimulated platelets is important in haemostasis, and partly because platelets can be used as models to investigate the actions of prostaglandins (PGs) at a cellular level¹. The effects of different PGs on platelets are diverse: PGE₁ is a potent inhibitor of platelet aggregation² with a K_i value around 30 nM and PGD₂ is an even more effective inhibitor of aggregation of human platelets, but not those of some other species^3,4. PGE₂ inhibits platelet aggregation at high concentrations (> 1 × 10⁻⁶ M), and there is some controversy as to whether lower concentrations enhance aggregation⁵. When human platelets are stimulated by collagen they synthesise PGE₂ from arachidonic acid⁶ and the cyclic endoperoxide intermediates in the biosynthesis of PGE₂ exert a direct aggregating effect^7,8. Synthetic derivatives of PGE₂ can also induce the aggregation of human platelets⁹, but PGE₂ itself has never been found to induce aggregation directly.