Molecular Cloning of Prostacyclin Synthase from Bovine Endothelial Cells

Abstract

Prostaglandin endoperoxide PGH₂ is at the crossroads of arachidonate metabolism, for it is the precursor of substances with opposing biological properties, thromboxane A₂ and prostacyclin. Thromboxane A₂ produced from PGH2 by the platelets is a powerful contractor of large blood-vessels and induces platelet aggregation. On the other hand, prostacyclin produced from PGH₂ by the vessel wall is a powerful vasodilator and the most potent natural occurring inhibitor of platelet aggregation. An imbalance in the thromboxane A₂: prostacyclin ratio may provide an explanation as to some of the changes occurring in various pathological situations including thrombosis and ischemia (1). The rearrangement of PGH₂ to thromboxane A₂ and prostacyclin is catalyzed by thromboxane synthase and prostacyclin synthase, respectively. New approaches to the therapy of such diseases are being sought by developing drugs that tilt the balance in favor of prostacyclin, either by inhibiting thromboxane synthase or protecting prostacyclin synthase. However, the molecular mechanism of these enzyme reactions still remain to be elucidated.