Metabolism of 6-ketoprostaglandin F1 alpha and prostacyclin to 6,15-diketo-13,14-dihydroprostaglandin F1 alpha-like material in cats and rabbits.

Using previously described radioimmunoassays for 6-ketoprostaglandin F1 alpha and 6,15-diketo-13,14-dihydroprostaglandin F1 alpha, plasma levels of these two products of degradation of prostacyclin (prostaglandin I2) were monitored in cats and rabbits. It was shown that both exogenous prostaglandin I2 and 6-ketoprostaglandin F1 alpha could be rapidly converted to 6,15-diketo-13,14-dihydroprostaglandin F1 alpha immunoreactivity, 6-ketoprostaglandin F1 alpha to an even somewhat larger extent. This difference in conversion could be explained by competing mechanisms which could delay or hinder the access of prostaglandin I2 to the sites of metabolism by 15-hydroxyprostaglandin dehydrogenase. The 6-ketoprostaglandin F1 alpha and 6,15-diketo-13,14-dihydroprostaglandin F1 alpha immunoreactivities were further characterized in two different thin-layer chromatographic systems and were shown to co-chromatograph exclusively with their respective standards. Similar results were obtained when tritium-labeled prostaglandin I2 or 6-ketoprostaglandin F1 alpha were infused into cats. Extracts of plasma samples taken at different time intervals after the infusion were submitted to thin-layer chromatography. The radioscans of the chromatograms showed two consistent peaks, one co-chromatographing with authentic 6-ketoprostaglandin F1 alpha and the other one with 6,15-diketo-13,14-dihydroprostaglandin F1 alpha. After infusion of 6-ketoprostaglandin F1 alpha the conversion to the 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha-like product occurred somewhat faster than after infusion of prostaglandin I2. We conclude that, under in vivo conditions in the two species investigated, 6-ketoprostaglandin F1 alpha can be rapidly and effectively metabolized by 15-hydroxyprostaglandin dehydrogenase.