Metabolism of prostacyclin: formation of an active metabolite in the liver.
Hepatic metabolism of prostacyclin (PGI2) results in the formation of several biological inactive lipids and one product that has the chromatographic and biological properties of 6-keto-PGE1; the latter, unlike prostacyclin, is stable. Further, authentic 6-keto-PGE1, like PGI2, escapes pulmonary degradation and is a potent inhibitor of platelet aggregation. It could be generated from either prostacyclin or its inactive hydrolysis product 6-keto-PGF1 alpha via the 9-hydroxyprostaglandin dehydrogenase pathway, which has been identified in the liver and kidney. The prolonged biological activity of PGI2, which is difficult to explain in view of its inherent instability, may derive from transformation of PGI2 to 6-keto-PGE1. These studies raise the question: What, if any, of the effects of prostacyclin on platelets and the circulation are dependent on its conversion to 6-keto-PGE1?
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D011464:Epoprostenol / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits
D011453:Prostaglandins; D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D006911:Hydroxyprostaglandin Dehydrogenases; D000527:Alprostadil