Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGF1 alpha in rat.
The in vivo metabolism of 6-keto PGF1 alpha was investigated in rats. Following continuous intravenous infusion for 14 days the urinary metabolites were isolated and identified. A substantial amount of unchanged 6-keto PGF1 alpha was recovered in the urine. The metabolic pattern very closely resembles that of PGI2 in rats. Metabolites were found which represented 15-dehydrogenation, beta-oxidation, omega and omega-1-hydroxylation and oxidation. Previous work showed that 6-keto PGF1 alpha is very poorly oxidized by 15-PGDH. We administered 15-[H3]-PGI2 and 15-[H3]-6-keto PGF1 alpha to rats and measured urinary tritiated water as an index for in vivo 15-PGDH activity. The results showed that PGI2 and 6-keto PGF1 alpha were both oxidized to the 15-keto product, although the rate of oxidation of PGI2 was greater than that of 6-keto PGF1 alpha. We concluded that the administered PGI2 was oxidized by 15-PGDH before hydrolysis to 6-keto PGF1 alpha. A portion of the dose is probably hydrolzyed before 15-dehydrogenation.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D011464:Epoprostenol / Q000008:administration & dosage / Q000378:metabolism*; D006868:Hydrolysis; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000008:administration & dosage / Q000652:urine*; D051381:Rats
D011453:Prostaglandins; D011460:Prostaglandins F; D011464:Epoprostenol; D006911:Hydroxyprostaglandin Dehydrogenases