SEARCH · PubMed Health

Results for “MONOAMINE OXIDASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1968

The distribution of monoamine oxidase and alpha-glycerophosphate dehydrogenase in pig brain.

Activities of the enzymes monoamine oxidase (EC 1.4.3.4), alpha-glycerophosphate dehydrogenase (EC 1.1.99.5) and cytochrome oxidase (EC 1.9.3.1) were determined in homogenates and in the mitochondrial fraction prepared from individual regions of pig brain. The variation in the activity of alpha-glycerophosphate dehydrogenase paralleled that of cytochrome oxidase, but this was not the case with monoamine oxidase. The differences in the activities of the enzymes among homogenates of the various regions of the brain persisted in mitochondria prepared from these homogenates. The purification of these three enzymes paralleled each other when mitochondria were prepared, suggesting that the three enzymes are bound to the same particles.

Animals↗

PubMed1985

Participation of brain monoamine oxidase B form in the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: relationship between the enzyme inhibition and the neurotoxicity.

A neurotoxin for nigrostriatal dopaminergic neurons, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its oxidized metabolite, 1-methyl-4-phenylpyridine (MPP+), both dose-dependently inhibited rat striatal and forebrain monoamine oxidase (MAO) activity with monoamine oxidase A (MAO-A) selectively reversible (competitive, Ki = 4.5 and 2.0 microM) inhibition. A comparison of the Ki values indicated the affinity of MPP+ for MAO-A to be greater than that of MPTP. MPTP inhibited monoamine oxidase B (MAO-B) with both a reversible (competitive, Ki = 116 microM) and an irreversible time-dependent component, but inhibition by MPP+ was reversible and competitive (Ki = 180 microM). These results, together with previous findings on metabolism of MPTP to MPP+ by brain MAO-B, suggest that MPP+ is a simple inhibitor of MAO-A and MAO-B, but MPTP might be a 'suicide substrate' inhibitor for MAO-B.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1981

Coupling of dopamine oxidation (monoamine oxidase activity) to glutathione oxidation via the generation of hydrogen peroxide in rat brain homogenates.

Homogenates of perfused rat brain generated oxidized glutathione from reduced glutathione during incubation with dopamine or serotonin. This activity was blocked by pargyline, a monoamine oxidase inhibitor, or by catalase, a scavenger of hydrogen peroxide. These results demonstrate formation of hydrogen peroxide by monoamine oxidase and the coupling of the peroxide to glutathione peroxidase activity. Oxidized glutathione was measured fluorometrically via the oxidation of NADPH by glutathione reductase. In the absence of added dopamine or serotonin, a much smaller amount of reduced glutathione was oxidized; this activity was blocked by catalase, but not by pargyline. Therefore, endogenous production of hydrogen peroxide, not linked to monoamine oxidase activity, was present. These results indicate that glutathione peroxidase (linked to hexose monophosphate shunt activity) can function to eliminate hydrogen peroxide generated by monoamine oxidase and other endogenous sources in aminergic neurons.

Animals↗

PubMed1985

N-nitrosodialkylamines do not function as substrates for liver monoamine oxidase.

Since reports in the literature [Rowland, I.R., Lake, B. G. & Gangolli, S. D. (1980) Mutat. Res. 72, 63-72] have implicated hepatic monoamine oxidase (EC 1.4.3.4) in the activation of N-nitrosodialkylamines to mutagens, it is of basic pharmacological and biochemical interest to determine if these compounds could serve as substrates for this enzyme. The dialkylnitrosamines N-nitrosodiethylamine, N-nitrosodimethylamine, and N-nitrosodibenzylamine were tested and found not to be substrates, competitive inhibitors, or irreversible inhibitors of liver monoamine oxidase. Thus, any role for monoamine oxidase participation in the mutagenic activation of these compounds must be subsequent to an initial conversion of these compounds to their respective secondary amines.

Animals↗

PubMed1986

Modification of serotonergic and noradrenergic neurotransmissions by repeated administration of monoamine oxidase inhibitors: electrophysiological studies in the rat central nervous system.

The net effect of repeated administration of monoamine oxidase inhibitors (MAOI) on central serotonergic (5-HT) and noradrenergic (NE) neurotransmissions was studied by assessing the responsiveness of hippocampal pyramidal neurons to microiontophoretically applied 5-HT and NE and the response of these neurons to the electrical activation of the 5-HT and NE ascending pathways. Brain monoamine oxidase (MAO) activity as well as the levels of 5-HT, NE and their metabolites were determined in order to verify the biochemical effects of the drugs administered. Twenty-one-day treatments with clorgyline and deprenyl inhibited very selectively MAO-A and MAO-B, respectively, whereas a treatment with phenelzine inhibited both forms of the enzyme. Whole brain concentrations of 5-HT and NE were increased by the antidepressant drugs clorgyline and phenelzine whereas deprenyl, an MAOI type B ineffective in endogenous depression, increased only NE levels after a 21-day treatment. The responsiveness of hippocampal pyramidal neurons to 5-HT was decreased by the long-term clorgyline treatment, but not by deprenyl and phenelzine, whereas that to NE was not altered by any of the treatments. The suppression of firing of these same neurons induced by the stimulation of the 5-HT pathway was increased by clorgyline and phenelzine, but not by deprenyl. The effect of the stimulation of the dorsal NE bundle was not modified by any of the treatments. These data show that prolonged inhibition of MAO-A, but not that of MAO-B, results in an enhanced 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1990

Hydrogen peroxide production by monoamine oxidase in isolated rat-brain mitochondria: its effect on glutathione levels and Ca2+ efflux.

H2O2 production and accumulation during incubation of isolated rat-brain mitochondria with substrates of monoamine oxidase A and B were investigated. All substrates gave rise to an accumulation of H2O2 which was inhibited by malate + pyruvate or isocitrate, consistent with a need for mitochondrial NADPH to maintain glutathione in the reduced state. However, in the absence of these additions the level of reduced glutathione decreased only by about 30%, indicating that only a fraction of the mitochondrial glutathione pool was accessible to the glutathione peroxidase and glutathione reductase activities responsible for the continuous removal of H2O2 generated by monoamine oxidase. The H2O2 accumulation was also inhibited by externally added reduced glutathione or NADPH but not NADH. External NADPH was oxidized by added oxidized glutathione but not alpha-ketoglutarate + NH4+. These results suggest that the removal of H2O2 generated by monoamine oxidase proceeds by way of special fractions of glutathione peroxidase and glutathione reductase that are located in the intermembrane space of mitochondria in such a way that they can react with both intra- and extra-mitochondrial glutathione and NADPH, possibly at the contact sites between the inner and outer mitochondrial membranes. Evidence is also presented that H2O2 generated by monoamine oxidase enhances Ca2+ release from mitochondria and may thus function as a regulator of mitochondrial Ca2+ efflux.

Animals↗

PubMed1971

Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type.

1. When rat brain or superior cervical ganglion monoamine oxidase was incubated with increasing concentrations of clorgyline, using tyramine as substrate, the inhibition of the enzyme could be represented by a pair of sigmoidal curves joined by a horizontal region where inhibition was constant. Tyramine appeared to be metabolized by two enzymes, one of which was highly sensitive to clorgyline, designated A, whereas the other enzyme, designated B, was less sensitive to clorgyline.2. The ratio of A/B activity for brain was 6/4 while in the ganglion it was 9/1.3. When the experiments were repeated using noradrenaline as the substrate, the inhibition of the enzyme followed a simple sigmoidal curve where deamination was inhibited by low concentrations of clorgyline as observed with enzyme A.4. We conclude that tyramine is deaminated by both A and B enzymes whereas noradrenaline is deaminated only by enzyme A, the enzyme which is most active in the ganglion. Our observations are consistent with the hypothesis that a specific intraneuronal monoamine oxidase plays an important role in the catabolism of noradrenaline in sympathetic nerves.

Animals↗

PubMedDate not supplied

[The effect of bacterial endotoxin on the activity of liver mitochondria monoamine oxidase].

An increase of lipid peroxidation and a decrease of the monoamine oxidase (EC 1.4.3.4) activity were found in mice liver mitochondria within 9 hrs of intoxication developed after administration of bacterial endotoxin at a dose corresponding to its LD50. The decrease in the monoamine oxidase activity appears to occur due to some alteration of the enzyme substrate specificity as well as to its partial liberation from mitochondrial membrane.

Animals↗

PubMed1991

[3H]harman binding experiments. I: A reversible and selective radioligand for monoamine oxidase subtype A in the CNS of the rat.

Harman (1-methyl-beta-carboline) is an endogenous compound with neurotropic properties in rats and humans. In a novel in vitro binding assay, the binding site of [3H]harman has been characterized in the rat crude mitochondrial (P2) fraction. The binding was saturable and reversible. Only a single high-affinity binding site was detected by kinetic, saturation, and displacement analyses in the cerebral cortex of the rat. The linear Scatchard plots revealed equilibrium dissociation constant (KD) values of approximately 2.5 nM at 0 degrees C, approximately 9 nM at 23 degrees C, and approximately 30 nM at 37 degrees C. Among six CNS regions (hypothalamus, hippocampus, cerebral cortex, striatum, cerebellum, and spinal cord), the highest density of binding sites (Bmax) was determined in the hypothalamus (approximately 5.5 pmol/mg of protein) and the lowest in the spinal cord (approximately 2.0 pmol/mg of protein). Several drugs known to affect serotonergic, adrenergic, dopaminergic, cholinergic, or GABAergic neurotransmission inhibited specific binding at best in the micromolar range. In contrast, potent and selective inhibitors of monoamine oxidase subtype A were active in the lower and middle nanomolar range. The displacing potency (apparent Ki) of substrates and inhibitors of monoamine oxidase correlated positively and highly significantly with the corresponding values of the inhibition of monoamine oxidase activity of subtype A (r = 0.92, p less than 0.001, n = 17) but not of subtype B (r = -0.47, p greater than 0.05, n = 15). In conclusion, [3H]harman was identified as a specific ligand of the active site of the A subtype of monoamine oxidase in rat brain.

Animals↗

PubMedDate not supplied

Brain and liver monoamine oxidase type A and type B activity in alcoholics and controls.

Monoamine oxidase activity in human postmortem brain and liver samples was measured in a group of patients with a prior history of alcoholism and compared to a control group with no prior history of alcoholism. Liver samples from patients with a prior history of alcoholism showed significantly lower monoamine oxidase activity with both phenylethylamine and serotonin as substrates. Postmortem brain samples, however, were not different in the two groups.

Adult↗

PubMed1998

Oxidation of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine, a 1-amino analog of MPTP, by type A and B monoamine oxidase.

A 1-amino analog of MPTP, 1(N)-amino-4-phenyl-1,2,3,6-tetrahydropyridine, was synthesized and the oxidation was examined using human synaptosomal mitochondria as sources of type A and B monoamine oxidase. An oxidation product, 1-amino-4-phenylpyridinium ion, was quantified by high-performance liquid chromatography-fluorometric detection. The amino analog was a substrate of both type A and B monoamine oxidase and the oxidation depended linearly on the enzyme amount and the reaction time with an optimal pH around 7.5. After the systemic injection of the amino analog in C57/black mice for one week, 1-amino-4-phenylpyridinium ion was detected in the brain. 1(N)-Amino-4-phenyl-1,2,3,6-tetrahydropyridine was proved to be cytotoxic to pheochromocytoma PC12 cells, and it may be a new neurotoxin bioactivated through the oxidation by type A and B monoamine oxidase.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited.

Many inhibitors of monoamine oxidase, particularly those developed during the past three decades, are often referred to as being "selective" for one or other isoform of the enzyme. However true this may be, selectivity within the EC 1.4.3.4 family does not preclude the possibility of interactions of these drugs with other proteins unrelated to monoamine oxidase. Indeed, evidence exists which either suggests or demonstrates directly that many of these inhibitors do interact with, and affect the behaviour of, other enzymes, receptor systems and uptake pumps, with potentially interesting consequences, desirable or otherwise, for the patient or the pharmacologist. An overview of many such interactions, and speculation upon some of the possible consequences, are provided in this review.

Animals↗

PubMed1976

Monoamine oxidase activity in rat erythrocytes: evidence for its localization in reticulocyte mitrochondria.

During growth of young rats, monoamine oxidase activity in erythrocyte membrane preparations decreases more rapidly than reticulocyte concentrations in the respective blood samples. Since reticulocytes lose their mitochondria prior to the substantia reticulo-filamentosa, the non-linear correlation between monoamine oxidase activity and reticulocyte counts indicates that erythrocyte monoamine oxidase is located in reticulocyte mitochondria.

Animals↗

PubMed1980

[State of serotonin--monoamine oxidase and histamine--diamine oxidase systems in circulating blood in ischemic strokes].

The serotonin-monoamine oxidase and histamine-diamine oxidase systems in the arteria and venous blood of the brain were examined in 65 patients with ischemic cerebral stroke. The examinations have shown that in the acute period of the disease the metabolism of serotonin and histamine is disturbed, the degree and the character of these disturbances depending substantially on the stroke clinical manifestations, process localization and the disease outcome. In infarctions in the large hemispheres without the secondary stem syndrome, the changes of the amine metabolism are determined by the state of the enzymes inactivating them. In patients with the secondary stem syndrome, the monoamine oxidase content in the blood leaving the brain is lowered, the methylation processes are activated, and the histamine level decreased, while the serotonin level is high. In cases of primary affection of the brain stem and the lethal outcome of the disease the blood levels of serotonin and histamine are high. Use of serotonin antagonists in ischemic stroke and antihistaminic drugs in primary affection of the brain stem is substantiated.

Adrenocorticotropic Hormone↗

PubMed2005

Low sodium intake induces an increase in renal monoamine oxidase activity in the rat. Involvement of an angiotensin II dependent mechanism.

AIMS: The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT1 receptor blockade on renal dopamine metabolism by monoamine oxidase. METHODS: Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT1 receptor antagonist, 20 mg kg(-1) bwt day(-1), NS + Los); 4, LS receiving Los (LS + Los). RESULTS: Urinary dopamine excretion was lower in LS than in NS rats (543 +/- 32 vs. 680 +/- 34 ng day(-1) 100 g(-1) bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 +/- 328 vs. 3081 +/- 681 ng day(-1) 100 g(-1) bwt and 1.90 +/- 0.5 vs. 5.7 +/- 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue(-1) h(-1): NS 7.66 +/- 0.52; LS 9.82 +/- 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 +/- 0.49 nmol mg tissue(-1) h(-1), P < 0.01, vs. LS). CONCLUSIONS: We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT1 receptors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

No association between Parkinson's disease and monoamine oxidase A and B gene polymorphisms.

Parkinson's disease (PD) is thought to be caused by a combination of unknown environmental, genetic and degenerative factors. Among these factors, monoamine oxidase has been considered as a possible factor in the pathophysiology of Parkinson's disease. We have carried out allelic association studies of PD with monoamine oxidase type A (MAOA) and monoamine oxidase type B (MAOB) gene loci using dinucleotide repeat polymorphisms. Distributions of all alleles at MAOA and MAOB gene loci were almost similar in patients and controls. Contrary to previous reports, our findings could not support the hypothesis that susceptibility to PD is associated with MAOA or MAOB polymorphism.

Adult↗

PubMed1987

A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition.

The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self-stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase.

Animals↗

PubMed1994

Inhibition of monoamine oxidase from bovine retina by beta-carbolines.

The behaviour of some beta-carboline derivatives as inhibitors of monoamine oxidase has been studied in bovine retina. Inhibition was found not to show any significant time dependence. Di- and tetrahydro-beta-carbolines were shown to behave as reversible and competitive inhibitors. In contrast, the fully unsaturated beta-carbolines harmane, harmine and harmaline, which showed deviation from linearity at high substrate concentrations, behaved as tight-binding inhibitors. In these cases, the concentration of the enzyme and the inhibitor were of the same order. This was confirmed by the Ki values for these compounds in the nanomolar concentration range. Consistent with this was that inhibition was only partly reversed by dialysis for 18 h at 4 degrees C, although complete reversal was observed after dialysis for the same period at 37 degrees C. Structure-activity relationships indicated that substitution of a methoxy group at the C7 position of the aromatic ring is determinant for this tight-binding behaviour; a substitution of this group at the C6 position greatly reduced inhibition. Since beta-carbolines have been reported to be formed endogenously, this suggests that they might have important physiological actions on monoamine oxidase activity in-vivo. In contrast, all the beta-carbolines investigated in this study had low potencies as inhibitors of monoamine oxidase B.

Animals↗