Search results for "Metyrapone"
showing 10 items of 18 documents
Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity
1983
Plasma ACTH levels after oral ingestion of 2 g metyrapone at 24.00 hours in six healthy subjects were higher after pretreatment with zimelidine (300 mg) in comparison to placebo. Since zimelidine is a relatively selective serotonin reuptake inhibitor its action on hypothalamic-pituitary-adrenal (HPA) activity suggests that serotonin is a potent stimulator of ACTH release. The ratio of cortisol to 11-deoxycortisol was taken as a measure of 11-hydroxylase activity, which indicates biological activity of secreted ACTH. These cortisol/11-deoxycortisol ratios were significantly increased after zimelidine treatment, when compared to placebo. Both the ACTH response and the cortisol/11-deoxycortiso…
Morphological and biochemical effects of glucocorticoids in chick embryo hepatocytes during development
1988
Abstract The administration in ovo of hydrocortisone-21-phosphate caused, in chick embryo liver, a reduction of the number of hepatocytes which can be isolated from 1 mg dry weight of liver and a marked increase of their size. Moreover, the treatment diminished the incorporation of thymidine into acid-insoluble fraction in these cells whilst it augmented the content of protein, RNA, DNA and the level of thymidine kinase/cell. These effects were highest at 8–10 days, then declined with the age, disappearing after 18th day of incubation. Similar effects were obtained by injecting other glucocorticoids or ACTH. Combined treatment with metopirone abolished the effects found with ACTH, but did n…
Kinetic experiments on the binding of metyrapone to liver microsomes
1969
Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …
Enzymic control of irreversible binding of metabolically activated benzo(a)pyrene in perfused rat liver by monooxygenase activity.
1977
Addition of [3H]-benzo(a)pyrene to the perfusion medium of isolated rat livers results in irreversible binding of radioactivity to DNA, RNA and protein. Binding to DNA accounted for about 0.1% of the total radioactivity which was bound in livers from animals treated with oil or saline and was increased by a factor of 3–5 after pretreatment of the animals with β-naphthoflavone or with phenobarbital. When the inhibitiors of monooygenase activity, α-naphthoflavone or metyrapone, were present in the perfusion medium, irreversible binding was reduced in livers from both β-naphthoflavone- and phenobarbital-pretreated animals, irrespective of the inhibitor used.
On the spectral intermediate at 440 nm formed during mixed function substrate oxidation.
1974
Abstract The spectral shoulder formed at 440 nm in microsomes oxidising hexobarbital and other drugs has been investigated and some of its properties characterised. Hexobarbital, pentobarbital, ethylmorphine and barbital produce this shoulder, while acetanilide, aniline, desmethylimipramine, imipramine, metyrapone and SKF 525-A do not. The formation of the 440 nm shoulder depends on the presence of NADPH and oxygen and is reduced in size when NADH is also present. At saturating substrate concentrations the size of the 440 nm shoulder is correlated to the cytochrome P-450 content. The hexobarbital induced shoulder can be inhibited by drug metabolism inhibitors such as metyrapone, imipramine …
The cytotoxicity of mitomycin C and Adriamycin in genetically engineered V79 cell lines and freshly isolated rat hepatocytes
1995
The objective of the present study was to investigate the cytotoxicity of Adriamycin (ADR) and mitomycin C (MMC) in tumor and non-tumor cells with respect to the role of cytochrome P450 (P450). Therefore, genetically engineered V79 Chinese hamster fibroblasts expressing only single enzymes of P450 were used. SD1 and XEM2 cells expressed rat P450IIB1 and P450IA1, respectively, whereas the V79 parental cells contained no detectable P450 levels. The cytotoxicity of ADR and MMC in the V79 cell system was compared with that in freshly isolated hepatocytes from phenobarbital (PB-hepatocytes)- and beta-naphthoflavone (beta NF-hepatocytes)-induced rats. Following 24 h of exposure to ADR equal cytot…
Kinetic experiments on the synergistic effect of NADH on microsomal drug oxidation.
1974
Abstract1. The synergistic effect of NADH on the NADPH-dependent mixed function oxidation of p-nitroanisole and hexobarbital can be measured both photometrically and by following the substrate-induced oxygen consumption. The increase in reaction rate is about 50% and lasts as long as NADH is present in the microsomal suspension.2. The oxidation of added NADH is increased by hexobarbital, ethylmorphine and SKF 525-A. Lineweaver-Burk transformation of the NADH oxidation rates yields straight lines for xenobiotic substrates suggesting Michaelis constants similar to those obtained from metabolic experiments. NADH oxidation in the absence of NADPH is about half as rapid as in its presence.3. Som…
Metabolism of metyrapone by a soluble enzyme system in rat liver.
1970
The formation of a metabolite of metyrapone by an oxygen sensitive soluble enzyme system in rat liver 105,000×g supernatant has been demonstrated. Enzyme activity requires the intact keto function of metyrapone.
Differential inhibition of biphenyl hydroxylation in perfused rat liver
1978
A differential inhibition of biphenyl hydroxylation by alpha-naphthoflavone and metyrapone was observed in isolated perfused rat liver. alpha-Naphthoflavone inhibited 2- and 4-hydroxylation in livers from beta-naphthoflavone-pretreated animals but had no effect on both reactions in livers from phenobarbital-pretreated animals. Metyrapone inhibited 2- and 4-hydroxylation in phenobarbital-stimulated livers, but only insignificant inhibition of 2-hydroxylation and a slight enhancement of 4-hydroxylation by metyrapone was observed in beta-naphthoflavone-stimulated livers. Conjugation of 2-hydroxybiphenyl and 4-hydroxybiphenyl by isolated perfused livers was also studied. 4-Hydroxybiphenyl prefe…
Action of metyrapone on the redox state of free nicotinamide-adenine dinucleotide and on oxygen consumption of perfused rat livers and isolated mitoc…
1971
Metyrapone [2-methyl-1,2-bis-(3-pyridyl)-1-propanone] in a concentration of 5 mM increased the lactate/pyruvate ratio and theΒ-hydroxybutyrate/ acetoacetate ratio in the perfusion fluid of the isolated rat liver by a factor of 6 indicating a considerable shift in the ratio of free [NAD]/[NADH] in both the cytoplasmic and the mitochondrial compartment. Oxygen uptake of the isolated liver was decreased to about one half. The onset of the inhibitory effect on the respiration of the isolated organ was immediate. The inhibition lasted for at least 1 h.