前列环素的代谢。III. 大鼠尿中6-酮基前列腺素F1α的代谢产物谱。

Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGF1 alpha in rat.

作者信息

Sun F F, Taylor B M, Sutter D M, Weeks J R

出版信息

Prostaglandins. 1979 May;17(5):753-9. doi: 10.1016/s0090-6980(79)80047-7.

Abstract

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.

摘要

在大鼠体内研究了6-酮基前列环素F1α（6-keto PGF1α）的代谢情况。连续静脉输注14天后，分离并鉴定了尿液中的代谢产物。尿液中回收了大量未变化的6-酮基前列环素F1α。其代谢模式与大鼠体内前列环素（PGI2）的代谢模式非常相似。发现的代谢产物表现为15-脱氢、β-氧化、ω和ω-1-羟基化及氧化。先前的研究表明，6-酮基前列环素F1α很难被15-前列腺素脱氢酶（15-PGDH）氧化。我们给大鼠注射15-[H3]-前列环素（15-[H3]-PGI2）和15-[H3]-6-酮基前列环素F1α，并测量尿中氚化水作为体内15-PGDH活性的指标。结果表明，前列环素和6-酮基前列环素F1α均被氧化为15-酮产物，尽管前列环素的氧化速率大于6-酮基前列环素F1α。我们得出结论，所注射的前列环素在水解为6-酮基前列环素F1α之前被15-PGDH氧化。一部分剂量可能在15-脱氢之前就被水解了。