Metabolism of prostaglandin E analogs in guinea pig and rat liver microsomes

Tritium-labelled 16,16-dimethyl-PGE2, 9-methylene-PGE2 (9-deoxo-16,16-dimethyl-9-methylene-prostaglandin E2) and tetranor-9-methylene-PGE2 were incubated with guinea pig liver microsomes. All three compounds were converted to omega-oxidized products in yields of a few per cent. In addition, from incubations with 9-methylene-PGE2 and tetranor-9-methylene-PGE2 were also obtained metabolites with the methylene group transformed into a dihydrodiol. In a comparative study with rat liver microsomes, it was found that these converted tetranor-9-methylene-PGE2 in a 50 per cent yield to omega-oxidized products. Finally, 20.000 X G supernatants from guinea pig and rat liver were compared with respect to omega-oxidation. The rat liver 20.000 X G supernatant was found to convert the substrate to the same extent as washed microsomes. By contrast, the guinea pig liver 20.000 X G supernatant was considerably more efficient than washed microsomes.