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J R Hoult

Publications and source records attributed to J R Hoult.

100 records · Page 6Linked to original sources
PubMed1978

Prostaglandin metabolism in rabbit kidney. Identification and properties of a novel prostaglandin 9-hydroxydehydrogenase.

Prostaglandin F2alpha is metabolized in 100 000 X g supernatants of rabbit kidney by a 15-hydroxydehydrogenase and a delta13-reductase to F-series metabolites, and byt a 9-hydroxydehydrogenase to E-series compounds. The reactions were measured by radiochemical and biological assays. The 15-hydroxydehydrogenase and 9-hydroxydehydrogenase are localised specifically in renal cortex, have optimal activity at alkaline ph and are effective over a wide range of substrate concentrations. The 9-hydroxydehydrogenase oxidises the 9-alpha hydroxyl group of prostaglandin F2alpha and F1alpha but not the 9-beta hydroxyl group of prostaglandin F2beta. This enzyme is also found in rabbit stomach and ileum, but not in 8 other organs examined; the 15-hydroxydehydrogenase has a wider distribution. Unlike other 9-hydroxydehydrogenase enzymes described to date, the enzyme prepared from rabbit kidney converts prostaglandin F2alpha directly to E2 in substantial amounts; this conversion may be of importance in renal homeostasis.

Animals↗
PubMed1978

Experimental hyperthyroidism in rats suppresses in vitro prostaglandin metabolism in lung and kidney.

Metabolism of prostaglandin (PG) F2alpha and PGE2 was depressed 40--62% in 100,000 g cytoplasmic supernatants of lungs and kidneys prepared from rats made hyperthyroid by 18 daily L(-) thyroxine injections (200microgram, s--c). These hyperthyroid rats had elevated serum thyroxine levels, cardiac hypertrophy and thyroid atrophy. There were no differences in soluble protein concentrations, NAD+ utilisation by endogenous enzymes and substrates, or in the NAD+ dependence of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) between the supernatants prepared from hyperthyroid rats and saline-injected controls. Thyroxine did not inhibit PG metabolism in vitro up to 260 micrometer. These results suggest that thyroxine specifically decreases intracellular levels of PG-metabolising enzymes, especially of the rate-limiting 15-PGDH. Metabolism of PGF2alpha and PGE2 by 15-PGDH was faster in smaller rats and declined with increasing animal weight. These studies imply that some of the clinical features of hyperthyroidism in man might be caused by deficiencies in PG metabolism.

Animals↗
PubMed1978

Sulphasalazine is a potent inhibitor of prostaglandin 15-hydroxydehydrogenase: possible basis for therapeutic action in ulcerative colitis.

Sulphasalazine is a potent and selective inhibitor in vitro of prostaglandin 15-hydroxydehydrogenase in rabbit colon (ID50 = 50 micrometer) and in several other organs of different species, but does not inhibit prostaglandin delta-13 reductase or microsomal prostaglandin synthesis from arachidonic acid. It is suggested that this action may underly the therapeutic usefulness of sulphasalazine in ulcerative colitis for the prevention of relapse.

Animals↗
PubMed1977

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.

Animals↗