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Biomedical subjects

R C Cottrell

Publications and source records attributed to R C Cottrell.

At least 37 records · Page 2Linked to original sources
PubMed1982

Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. II. Inhibition by substrates and inhibitors of monoamine oxidase.

1. The metabolism of dimethylnitrosamine (DMN) to formaldehyde by rat-hepatic postmitochondrial supernatant fractions has been compared with the activities of several cytochrome P-450-dependent mixed-function oxidase enzymes and the Ziegler mixed-function amine oxidase enzyme (EC 1.14.13.8). 2. A variety of monoamine oxidase (MAO, EC 1.4.3.4) inhibitors of diverse chemical structure inhibited the metabolism of DMN. In parallel studies a number of MAO substrates, but not their deaminated products, also inhibited DMN metabolism, whereas substrates of diamine oxidase were ineffective. 3. At concentrations which inhibited DMN metabolism several MAO substrates and inhibitors did not inhibit the N-oxidation of N, N-dimethylaniline and an inhibitor and an activator of the Ziegler enzyme had no corresponding effect on DMN metabolism. 4. The metabolism of DMN and a number of MAO enzyme activities were stable to storage under conditions where mixed-function oxidase enzymes were not. 5. These results are consistent with the suggestion that DMN may, at least in part, be metabolized by hepatic enzyme(s) not dependent on cytochrome P-450 and that a microsomal amine oxidase enzyme, unrelated to the Ziegler enzyme, may be involved in the hepatic degradation of this nitrosamine. The present data does, however, suggest a role for microsomal NADPH-cytochrome c reductase in hepatic DMN metabolism.

Amine Oxidase (Copper-Containing)↗
PubMed1982

Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. III. Effect of cobaltous chloride treatment.

1. The effects of CoCl2 administration to rats on xenobiotic metabolism, dimethylnitrosamine (DMN) metabolism to formaldehyde and methanol, and monoamine oxidase (MAO) enzyme activities in hepatic subcellular fractions have been studied. 2. CoCl2 treatment markedly decreased hepatic mixed-function oxidase enzyme activities and microsomal cytochrome P-450 content. In contrast, the N-oxidation of N, N-dimethylaniline and the activity of microsomal NADPH-cytochrome c reductase was unaffected. 3. The metabolism of DMN to formaldehyde by postmitochondrial supernatant fractions was decreased at substrate concn. of 0 . 5, 5 and 50 mM by CoCl2 treatment but the metabolism of 5 and 50 mM DMN to methanol was affected less. 4. CoCl2 had little effect on MAO activities in whole homogenates, but microsomal MAO activities were markedly inhibited. 5. The inhibition of microsomal MAO indicates that CoCl2 is not a specific inhibitor of cytochrome P-450-dependent biotransformations and consequently the inhibition of DMN metabolism is not evidence of a wholly cytochrome P-450-dependent process.

Animals↗
PubMed1982

Studies on the metabolism of dimethylnitrosamine in vitro by rat-liver preparations. I. Comparison with mixed-function oxidase enzymes.

1. The metabolism of dimethylnitrosamine (DMN) to formaldehyde by rat-liver preparations has been studied at substrate concn. of 0.5, 5 and 50 mM and compared with mixed-function oxidase enzyme activities. 2. The microsomal metabolism of low (0.5 and 5 mM) and high (50 mM) substrate concn. of DMN was differentially affected by acetone addition or KI treatment. 3. A series of heterocyclic compounds related to pyrazole were potent inhibitors of metabolism of 0.5 and 5 mM DMN at concn. which had little effect on mixed-function oxidase activities. In contrast, purine addition slightly stimulated the metabolism of low but not high concn. of DMN. 4. The results are consistent with the suggestion that multiple enzymic pathway(s) are involved in hepatic DMN metabolism and that some of these pathway(s) may be independent of cytochrome P-450.

Acetone↗
PubMed1982

Inhibition of dimethylnitrosamine metabolism by some heterocyclic compounds and by substrates and inhibitors of monoamine oxidase in the rat.

Pretreatment of rats with a number of nitrogen-containing heterocyclic compounds was found to inhibit markedly the metabolism of dimethylnitrosamine (DMN) in terms of both CO2 excretion and decline in blood DMN concentration. However, many of these compounds had either much less or no inhibitory effect on the in vivo metabolism to CO2 of a typical mixed-function oxidase substrate, aminopyrine. In addition, a number of model inhibitors of monoamine oxidase (MAO) activity also inhibited DMN metabolism in the intact animal, and a number of primary amines, known substrates of hepatic MAO, inhibited DMN metabolism but not that of aminopyrine in the isolated perfused liver system. These results, together with in vitro data and previously reported studies on the effect of MAO inhibitors and substrates on the mutagenicity of DMN, suggest that the metabolism and bioactivation of DMN may be in part mediated by a MAO type of enzyme activity.

Aminopyrine↗
PubMed1977

Some properties of the membrane-bound and solubilised forms of the protein disulphide isomerase of rat liver microsomes.

1. An improved method of measurement of the protein disulphide isomerase (protein disulphide-isomerase, EC 5.3.4.1) activity of microsomal preparations is described. 2. This enzyme is shown to be released from the membranes into solution in the ultracentrifuge. 3. Some of the properties of the enzyme in the membrane bound and soluble forms are described. 4. The results lead to the suggestion that the enzyme present in rough membrane is different from the present in smooth membrane as well as being differently situated in the membrane. 5. Some of the effects of sucrose on the activity of the membrane bound enzyme are consistent with the view that the membranes may undergo irreversible conformational changes during preparation and storage.

Animals↗
PubMed1977

Studies of the metabolic fate of p-hydroxybenzoic acid in male and female cats.

Metabolic studies conducted on p-hydroxybenzoic acid orally administered at dose levels of 13 and 26 mg/kg to male and female cats have shown that the compound is rapidly excreted in the urine exclusively in the form of the glycine conjugate p-hydroxyhippuric acid. Similar results were obtained following either single administration or 7-day treatment. The metabolite in the urine was characterised by thin-layer chromatography, amino acid analysis and mass spectrometry.

Amino Acids↗