Prostaglandin (PG) endoperoxides (
PGG2 and
PGH2) 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
PGE2, F2alpha, D2,
thromboxane A2 and their metabolites. PGX is less active in contracting rat fundic strip, chick rectum, guinea pig ileum and guinea pig trachea than are
PGG2 and
PGH2. PGX does not contract the rat colon. PGX is unstable in aqueous
solution and its antiaggregating activity disappears within 0.25 min on boiling or within 10 min at 37degrees C. As an inhibitor of human platelet aggregation induced in vitro by
arachidonic acid PGX was 30 times more potent than
PGE1. The enzymic formation of PGX is inhibited by 15-hydroperoxy
arachidonic acid (IC50 = 0.48 mug/ml), by spontaneously oxidised
arachidonic acid (IC 50 less than 100 mug/ml) and by
tranylcypromine (IC50 = 160 mug/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.