Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides

Abstract

Prostaglandin (PG) endoperoxides (PGG 2 and PGH 2) contract arterial smooth muscle and cause platelet aggregation. Microsomes from pig aorta, pig mesenteric arteries, rabbit aorta and rat stomach fundus enzymically transform PG endoperoxides to an unstable product (PGX) which relaxes arterial strips and prevents platelet aggregation. Microsomes from rat stomach corpus, rat liver, rabbit lungs, rabbit spleen, rabbit brain, rabbit kidney medulla, ram seminal vesicles as well as particulate fractions of rat skin homogenates transform PG endoperoxides to PGE- and PGF- rather than to PGX-like activity. PGX differs from the products of enzymic transformation of prostaglandin endoperoxides so far identified, including PGE 2, F 2α, D 2, thromboxane A 2 and their metabolites. PGX is less active in contracting rat fundic strip, chick rectum, guinea pig ileum and guinea pig trachea than are PGG 2 and PGH 2. PGX does not contract the rat colon. PGX is unstable in aqueous solution and its anti-aggregating activity disappears within 0.25 min on boiling or within 10 min at 37° C. As an inhibitor of human platelet aggregation induced in vitro by arachidonic acid PGX was 30 times more potent than PGE 1. The enzymic formation of PGX is inhibited by 15-hydroperoxy arachidonic acid (IC 50 = 0.48 μg/ml), by spontaneously oxidised arachidonic acid (IC 50 <100 μg/ml) and by tranylcypromine (IC 50 = 160 μg/ml). We conclude that a balance between formation by arterial walls of PGX which prevents platelet aggregation and release by blood platelets of prostaglandin endoperoxides which induce aggregation is of the utmost importance for the control of thrombus formation in vessels.