The Effects of Drugs and Steroid Hormones on the Enzymes of the Endoplasmic Reticulum

Parke, Dennis V.

doi:10.1007/978-1-349-01321-0_5

Cited by 5 publications

(3 citation statements)

References 114 publications

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“…He also suggested that induction of drug metabolizing enzymes was first preceded by a period of enzyme inhibition. Since steroids of all kinds, including corticosteroids, have been shown to increase the activity of microsomal drug-metabolizing enzymes (Conney 1967;Parke 1971) which also mediate the oxidative metabolism of steroids, it is possible that dexamethasone is able to enhance its own metabolism. The degree of enhancement is likely to be reflected in the increased urinary excretion of component IV and in the excretion of unchanged dexamethasone during the first days of a 4-day infusion.…”

Section: Discussionmentioning

confidence: 99%

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Studies on Intravenously Infused Dexamethasone in Sheep

Leish¹,

Panaretto²

1978

Aust. Jnl. Of Bio. Sci.

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Aust. J. Bioi. Sci., 1978, 31, 373-83 The metabolism of [1,2(n)-3Hldexamethasone intravenously infused for periods of 4 and S days was examined in four Merino wethers.On average 85·6±2·8 (s.e.m.) % of the total dose was recovered, 56·2±5·1 and 29·4±3·3% being excreted in urine and faeces respectively. In total 12·4 % of the dose was associated with the unconjugated steroid fraction which represented 22% of the total urinary radioactivity.Thin layer chromatography of the urinary unconjugated fractlon revealed, apart from dexamethasone, five major and three minor radioactive components designated as I, III, IV, V, VIII and II, VII, IX respectively. Approximately 83 % of the radioactivity associated with the unconjugated fractions was found in constituents more polar than dexamethasone with the radioactivity mainly confined to the principal metabolite IV, Rc = 0·24 (dexamethasone, Rc = 0·45;'cbloroform: formarnide 50:1). The urinary constituent VI, Rc = 0·37, was detected only -during-the second half of the 8-day infusion with the peak of excretion on day 6.During the first 30 h of [3Hldexamethasone administration the plasma radioactivity reached the level which remained relatively constant throughout the infusions. The initial high level of radioactivity detected in the plasma unconjugated fraction as well as dexamethasone during the first 24 h infusion declined over the next 2 days; this was followed by a small increase during the final period of infusions.The radioactivity of the plasma unconjugated fraction was distributed, apart from dexamethasone, into six constituents (I, III, IV, V, VIII and IX) which when analysed by thin layer chromatography appeared to be qualitatively similar to those found in urine.These results led to the conclusion that one or more products of dexamethasone metabolism might be biologically active and thus potentially important in inhibiting wool fibre growth in sheep.

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Section: Discussionmentioning

confidence: 99%

“…Kinetics of particular metabolizing enzymes [low Michaelis constants for the hydroxylation of steroids (Parke 1971); different substrate concentrations] probably determined the quantitative differences in urinary excretion between the 4-and 8-day infusions.…”

Section: Discussionmentioning

confidence: 99%

Studies on Intravenously Infused Dexamethasone in Sheep

Leish¹,

Panaretto²

1978

Aust. Jnl. Of Bio. Sci.

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“…This mixture includes the microsomal monooxygenases which are involved in the oxidation of both endogenous and exogenous chemical substrates to give more hydrophilic metabolic products. Mechanistic studies have confirmed or have implicated the formation of metabolically active arene oxide intermediates in this process and these reactive species are associated with cellular toxicosis (Parke 1972;Gillette 1975;Daly et al 1972;Jerina & Daly 1974). The investigation of the microsomal-mediated metabolism of chemical substrates is routinely carried out by incubating the chemical and the required cofactors with either the hepatic postmitochondrial supernatant (PMS) fraction or with a microsomal fraction obtained by further differential centrifugation (MDC) of the crude postmitochondrial supernatant.…”

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confidence: 99%

The detection of enzyme induction by rat liver microsomes prepared by isoelectric precipitation

Parkinson

Safe

1979

Journal of Pharmacy and Pharmacology

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A comparison was made of various indices of the hepatic drug‐metabolizing apparatus associated with the postmitochondrial supernatant, microsomes harvested by differential centrifugation, and microsomes harvested by isoelectric precipitation from control, phenobarbitone‐pretreated and 3‐methylcholanthrene‐pretreated rats. The metabolic capabilities and distinctions between control and induced rats for each of the three liver preparations compared favourably as determined by the concentration of cytochrome b5 and P‐450 and by the activity of NADPH‐cytochrome c reductase, 4‐dimethylaminoantipyrine N‐demethylase and aryl hydrocarbon (benzo[a]pyrene) hydroxylase. The results suggest that the relatively simple isoelectric precipitation technique is a useful alternative to the conventional method of differential centrifugation for the preparation of hepatic microsomes.

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On the biochemical mechanism of tumorigenesis in mouse skin

Pyerin

Hecker

1979

J Cancer Res Clin Oncol

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The Effects of Drugs and Steroid Hormones on the Enzymes of the Endoplasmic Reticulum

Cited by 5 publications

References 114 publications

Studies on Intravenously Infused Dexamethasone in Sheep

Studies on Intravenously Infused Dexamethasone in Sheep

The detection of enzyme induction by rat liver microsomes prepared by isoelectric precipitation

On the biochemical mechanism of tumorigenesis in mouse skin

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