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.
Steffenrud
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D015064:16,16-Dimethylprostaglandin E2 / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006900:Hydroxylation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats
D011458:Prostaglandins E; C049541:9-deoxy-16,16-dimethyl-tetranor-9-methyleneprostaglandin E2; C025505:meteneprost; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2