Enzymatic inactivation of 6-keto-prostaglandin E1 in vitro: comparison with prostaglandin E1.
The inactivation of 6-keto PGE1, a biologically active and stable metabolite of prostacyclin, was studied in 100,000 g cytosolic supernatants by bioassay on rat stomach strip (contraction) and human platelets (inhibition of ADP-induced aggregation). PGE1 was used as a reference compound. Both PGs were inactivated in supernatants from colon, kidney and liver of rat, rabbit and guinea-pig. Inactivation was time- and NAD+ -dependent and was generally greater for PGE1 than 6-keto-PGE1. The enzyme responsible for 6-keto-PGE1 inactivation in cytosolic supernatants is distinct from prostaglandin 15-hydroxydehydrogenase and 9-keto reductase, is not inhibitable by sulphasalazine-like drugs and its activity is recoverable after precipitation by ammonium sulphate. We conclude that 6-keto-PGE1 can be inactivated by enzymes with wide tissue distribution, but further studies are needed for identification of these novel enzymes and the products formed as well as to assess their significance in the intact animal.
D000527:Alprostadil / Q000031:analogs & derivatives; D000818:Animals; D003106:Colon / Q000201:enzymology; D004372:Ducks; D006168:Guinea Pigs; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D011458:Prostaglandins E / Q000378:metabolism*; D011817:Rabbits; D051381:Rats
D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D006911:Hydroxyprostaglandin Dehydrogenases; C035858:prostaglandin-E2 9-reductase; D000527:Alprostadil