Pathways of prostaglandin F2alpha metabolism in mammalian kidneys.

1 High-speed cytoplasmic supernatants of rat, rabbit, pig and guinea-pig kidneys were prepared and the metabolism of 10 mug/ml prostaglandin F(2alpha) labelled with [(3)H(1)-9beta]-prostaglandin F(2alpha) studied by thin layer radiochromatography and bioassay.2 The metabolism of prostaglandin F(2alpha) measured by radiochromatography parallels biological inactivation in all species except the rabbit.3 Kidneys metabolize prostaglandin F(2alpha) by two divergent pathways, yielding a mixture of prostaglandin E and F metabolites.4 15-Hydroxyprostaglandin dehydrogenase and prostaglandin Delta-13 reductase are present in all species in characteristic proportions. Thus prostaglandin F(2alpha) is metabolized sequentially to 15-keto prostaglandin F(2alpha) and 13,14-dihydro-15-keto prostaglandin F(2alpha). The rate and profile of formation of these metabolites is species-dependent.5 13,14-Dihydro-15-keto prostaglandin F(2alpha) is the principal prostaglandin F series metabolite in all species.6 Pig and guinea-pig kidney contain an unidentified enzyme which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro prostaglandin F(2alpha).7 Rat kidney contains a high concentration of a prostaglandin 9-hydroxy dehydrogenase which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro-15-keto prostaglandin E(2).8 Rabbit kidney contains a novel 9-hydroxydehydrogenase which oxidises prostaglandin F(2alpha) directly to E(2), thus producing a compound with more potent renal actions. The possible implications of this enzyme for kidney homeostasis are discussed.