Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides.
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.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism*; D001681:Biological Assay; D005753:Gastric Mucosa / Q000378:metabolism; D006736:Horses; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D012756:Sheep; D013552:Swine
D001095:Arachidonic Acids; D010545:Peroxides; D011453:Prostaglandins; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases