Circulating prostacyclin metabolites in the dog
The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of (11 beta-/sup 3/H)PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation.
- Research Organization:
- Department of Experimental Sciences I, Upjohn Company, Kalamazoo, Michigan
- OSTI ID:
- 5821967
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 224:3; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Epoxidation of prostacyclin in the rabbit kidney
Metabolic disposition of prostacyclin in humans
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTORADIOGRAPHY
BIOLOGICAL MATERIALS
BLOOD
BLOOD PLASMA
BLOOD VESSELS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
CHEMICAL ANALYSIS
CHROMATOGRAPHY
DOGS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLITES
ORGANS
PROSTAGLANDINS
SEPARATION PROCESSES
TRITIUM COMPOUNDS
VERTEBRATES