Tissue distribution and biliary excretion of prostacyclin metabolites in the rat. 1980

B M Taylor, and F F Sun

When tritium labeled prostacyclin (PGI2) or 6-keto PGF1 alpha were injected i.v. into rats, one-third of the dose appeared in the liver after 15 min. Significant levels of radioactivity (8--16%) were also found in the small intestine. These observations plus the prominant fecal excretion of PGI2 radioactivity suggest that PGI2 and/or its metabolites undergo biliary excretion and enterohepatic recirculation. We therefore investigated PGI2 excretion and metabolite composition of the bile in bile duct cannulated rats. After a single bolus i.v. injection of 11-[3H] PGI2 into these rats, an average of 37% of the administered radioactivity was excreted in the bile within 3 hr. A number of metabolites were detected in the bile. The major metabolites were isolated and identified as 2,3-dinor-6-keto-PGF1 alpha and 13,14-dihydro-2,3-dinor-6,15-diketo-PGF1 alpha-glucuronide which each accounted for approximately one-third of the radioactivity in the bile. Other metabolites include 6-keto PGF1 alpha, 13,14-dihydro-2,3-dinor-6,15-diketo-PGF1 alpha, 13,14-dihydro-2,3-dinor-6,15-diketo-20-carboxyl PGF1 alpha and 2,3,4,5,6-pentanor-PGF1 alpha-gamma-lactone. We conclude that the liver plays a pivotal role in the inactivation and disposition of prostacyclin. The predominate metabolic pathways occurring in the liver are probably beta-oxidation and glucuronic acid conjugation.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011453 Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Prostaglandin,Prostanoid,Prostanoids
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D005260 Female Females
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass

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