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PATHWAYS OF PROSTAGLANDIN F 2α METABOLISM IN MAMMALIAN KIDNEYS
Author(s) -
HOULT J.R.S.,
MOORE P.K.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb07555.x
Subject(s) - prostaglandin , kidney , metabolite , prostaglandin e , prostaglandin e2 , metabolism , chemistry , endocrinology , medicine , dehydrogenase , guinea pig , enzyme , biology , biochemistry
1 High‐speed cytoplasmic supernatants of rat, rabbit, pig and guinea‐pig kidneys were prepared and the metabolism of 10 μg/ml prostaglandin F 2α labelled with [ 3 H 1 ‐9β]‐prostaglandin F 2α studied by thin layer radiochromatography and bioassay. 2 The metabolism of prostaglandin F 2α measured by radiochromatography parallels biological inactivation in all species except the rabbit. 3 Kidneys metabolize prostaglandin F 2α by two divergent pathways, yielding a mixture of prostaglandin E and F metabolites. 4 15‐Hydroxyprostaglandin dehydrogenase and prostaglandin Δ‐13 reductase are present in all species in characteristic proportions. Thus prostaglandin F 2α is metabolized sequentially to 15‐keto prostaglandin F 2α and 13,14‐dihydro‐15‐keto prostaglandin F 2α . The rate and profile of formation of these metabolites is species‐dependent. 5 13,14‐Dihydro‐15‐keto prostaglandin F 2α 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 2α to 13,14‐dihydro prostaglandin F 2α . 7 Rat kidney contains a high concentration of a prostaglandin 9‐hydroxy dehydrogenase which converts 13,14‐dihydro‐15‐keto prostaglandin F 2α to 13,14‐dihydro‐15‐keto prostaglandin E 2 . 8 Rabbit kidney contains a novel 9‐hydroxydehydrogenase which oxidises prostaglandin F 2α directly to E 2 , thus producing a compound with more potent renal actions. The possible implications of this enzyme for kidney homeostasis are discussed.