Showing papers on "Monoamine oxidase B published in 1980"
TL;DR: Kinetic studies indicated that the Vmax of MAO B was increased in aging rat brain, whereas the Km was unaltered, and age‐related changes in total protein, MAO A, andMAO B were thus independent of each other.
Abstract: The activity of monoamine oxidase (MAO) was assayed in the brains of young adult (7-8 weeks old) and aging (95-104 weeks old) male Sprague-Dawley rats. When expressed per milligramme of tissue, total protein content was increased to a similar extent in whole brain and in all seven brain regions of the aging rat, whereas MAO A activity (assayed by using 5-hydroxytryptamine as substrate) was unchanged in whole brain but increased in the cerebellum, and fell in the brainstem, midbrain, hippocampus, and cortex; and MAO B activity (assayed by using beta-phenylethylamine as substrate) increased in whole brain and all regions, except the brainstem. Age-related changes in total protein, MAO A and MAO B were thus independent of each other. Kinetic studies indicated that the Vmax of MAO B was increased in aging rat brain, whereas the Km was unaltered. The increase in MAO B activity was restricted to the extrasynaptosomal mitochondrial fraction of the aging brain, whereas a reduction in MAO A activity was found in the intrasynaptosomal, but not the extrasynaptosomal mitochondrial fraction.
177 citations
115 citations
111 citations
TL;DR: Estimation of total activity developed by tissue or organ sheds a new light on the importance of each enzyme in body economy and shows skeletal muscle to be by far the most active whole body source ofMAO B, whilst the liver has the highest total and specific activity of MAO A.
106 citations
TL;DR: This is the first reported study of the antidepressant properties of L-deprenyl using a lower dose range, where both selective inhibition of type-B monoamine oxidase (MAO) would occur and the patient would be protected from the hypertensive cheese reaction.
87 citations
Journal Article•
TL;DR: Reduction in labeled serotonin binding caused by monoamine oxidase inhibitors is due to a decrease in the maximum number of specific binding sites with no change in the affinity of the binding sites for labeled serotonin.
Abstract: Rats were administered either monoamine oxidase inhibitors or serotonin uptake inhibitors for either 1, 4 or 16 days. The binding of [3H]serotonin to brain homogenates and the concentration of serotonin in brain was measured at these times. Treatment with inhibitors of serotonin uptake did not change the specific binding of [3H]serotonin in either cerebral cortex or hippocampus, nor did it produce any consistent alterations in the concentration of serotonin in the cerebral cortex. In contrast, monoamine oxidase inhibitors capable of inhibiting A-type monoamine oxidase significantly decreased [3H]serotonin binding after both 4 and 16 days of treatment; serotonin concentrations were significantly elevated at all time intervals. Inhibitors of B-type monoamine oxidase had no effect on either [3H]serotonin binding or serotonin concentrations in cerebral cortex. The reduction in labeled serotonin binding caused by monoamine oxidase inhibitors is due to a decrease in the maximum number of specific binding sites with no change in the affinity of the binding sites for labeled serotonin.
83 citations
68 citations
TL;DR: It is suggested that the imine formed on oxidation of the inhibitor by the flavin combines with an -SH group at the substrate binding site to form a thioaminoketal or thiohemiketal, and this structure is stabilized by noncovalent interactions in the native enzyme but becomes labile and dissociable when the enzyme is unfolded.
66 citations
TL;DR: The correlation between the A/B ratio present in different human brain regions and the sensitivity of dopamine oxidation to 10(-6)M deprenyl was 0.84, suggesting that all dopamine oxidation can be accounted for by the joint contribution of MAO A and B and that it is unnecessary to postulate a special form of the enzyme which metabolizes dopamine.
Abstract: Dopamine is predominantly oxidized by a (-)-deprenyl sensitive form of MAO in the human striatum, and (-)-deprenyl, acting at some suitably low selective inhibitory concentration may, therefore, be of benefit in Parkinson’s disease. 10-6M was the most effective (-)-deprenyl concentration in vitro for discriminating between the inhibition of MAO A and B. The correlation between the A/B ratio present in different human brain regions and the sensitivity of dopamine oxidation to 10-6M deprenyl was 0.84 (p < 0.001). This suggests that all dopamine oxidation can be accounted for by the joint contribution of MAO A and B and that it is unnecessary to postulate a special form of the enzyme which metabolizes dopamine. In the brain, the striatum has the highest proportion of MAO B, and in several cortical regions, relatively more dopamine is oxidized by MAO A. In other human tissues also the deprenyl sensitivity of dopamine oxidation correlated with the known A/B ratio, the placenta, lung and jejeunum having the lowest sensitivity and being the richest in MAO A. Km values for dopamine for MAO A and B are similar, 130 and 140 μM respectively, so that the proportion oxidized by the two forms should not vary with substrate concentration.
59 citations
44 citations
TL;DR: Mitochondria in the terminals of dopaminergic neurones have an even more pronounced enrichment in MAO A than the mitochondria obtained by osmotic lysis of a total brain synaptosomal preparation.
TL;DR: The limited studies of brain MAO activity in man fail to demonstrate differences between patients with schizophrenia and normal controls, and controlled for variables possibly influencing the blood enzyme activity, such as prior neuroleptic treatment.
Abstract: Monoamine oxidase (MAO) activity has been shown to be influenced by a variety of demographic, biologic, and other variables. Human platelet, plasma, and brain enzyme activities correlate with age and are higher in women. Brain catecholamines tend to decrease with age. The acute effects of ethanol on platelet MAO do not appear to be significant, but chronic ethanol ingestion could influence enzyme activity through a variety of possible mechanisms. Numerous drugs and hormones have been shown to alter platelet and tissue MAO. Heterogeneity of platelet size, density, age, and enzyme activity complicates the study of MAO in clinical populations. Newer platelet isolation techniques may diminish the variability due to platelet sampling. Studies of platelet MAO activity in schizophrenia require that careful attention be given to controlling for variables possibly influencing the blood enzyme activity, such as prior neuroleptic treatment. The limited studies of brain MAO activity in man fail to demonstrate differences between patients with schizophrenia and normal controls.
TL;DR: Oral intubation of styrene in adult male albino rats for 15 days produced a significant increase in serotonin and noradrenaline but no change in dopamine contents in brain, hinting at alterations in levels of these biogenic amines in the brain tissue.
TL;DR: Deamination of Bz (sensitive to 10(-7) M deprenyl) was a better indicator of MAO B activity than deamination of PEA at commonly used substrate concentrations; the divergence between PEA and Bz as MAO A and B substrates may be one reason for some of the apparent discrepancies in the behaviour ofMAO Aand B noted in a variety of tissues in the literature.
TL;DR: The basic principle underlying these models is that MAO inhibition leads to impaired regulation in many neurotransmitter systems and other cellular functions, yielding consquent deficits in the attenuation of responses to exogenous stimuli and to endogenous psychobiological changes.
Abstract: Monoamine oxidase (MAO) has many intraneuronal regulatory metabolic functions as well as detoxifying properties. Inhibition of the enzyme leads to rapid changes in the cellular concentrations of neurotransmitter amines and in the balance between different amines in neurons. Longer term alterations in MAO activity are accompanied by secondary, adaptational changes in neurotransmitter-related receptors, other enzymes, and additional cell functions in brain and other tissues. In addition, MAO inhibition is accompanied by marked changes in the sensitivity of the organism to some dietary constituents (e.g., tyramine, tryptophan, and other amines and amine precursors) as well as to many drugs (e.g., sympathomimetics, opiates, reserpine, and caffeine). While nearly complete MAO inhibition has been said to be required for direct behavioral changes to occur, partial MAO inhibition (reductions of 25-75 percent in enzyme activity) or selective inhibition of either the MAO-A or MAO-B form of the enzyme-especially after longer term inhibitor administration-lead to readily demonstrable alterations in the sensitivity of both animals and man to a variety of exogenous agents, and are also associated with a number of biological changes, including those involving neuroendocrine, blood pressure, and sleep mechanisms. These changes in cellular mechanisms and physiological functions may provide models for evaluating the significance of moderate (40 percent) mean reductions in platelet MAO activity found in chronic schizophrenic patients and some other psychiatric patient populations. The basic principle underlying these models is that MAO inhibition leads to impaired regulation in many neurotransmitter systems and other cellular functions, yielding consquent deficits in the attenuation of responses to exogenous stimuli and to endogenous psychobiological changes.
01 Jan 1980
TL;DR: The history of monoamine oxidase inhibitor (MAOI) use in psychiatry is a curious one and far from complete, but the possibility of using this combination to activate retarded schizophrenic patients and to treat depression suggested itself.
Abstract: The history of monoamine oxidase inhibitor (MAOI) use in psychiatry is a curious one and far from complete. The inspiration for our own use derived from the work of Chessin et al. (1956) who found that “marsalinizing” (treating with Marsilid, i.e., iproniazid) an animal before administering reserpine produced a paradoxical effect1. The animal rather than becoming sedated became hyperalert and active. Scott described these findings during a visit to Warner Laboratories as part of a discussion which dealt with the mode of action of reserpine. The possibility of using this combination to activate retarded schizophrenic patients and to treat depression suggested itself.
Journal Article•
TL;DR: The effect of (-)-deprenyl, a rapidly acting selective monoamine oxidase (MAO) B inhibitor, on the sleep and mood of six healthy young male adults was investigated and the only effect of the drug on mood was to decrease the level of alertness prior to sleep.
Abstract: The effect of (-)-deprenyl, a rapidly acting selective monoamine oxidase (MAO) B inhibitor, on the sleep and mood of six healthy young male adults was investigated. The drug was administered double-blind in a balanced cross-over design. The dose (5–10 mg/day for 3 days) was chosen to cause complete inhibition of MAO, a process which usually takes 1–2 weeks with conventional MAO inhibitors. The inhibition was monitored by measuring platelet MAO activity and phenylethylamine excretion. Urinary phenylethylamine concentration was raised in all subjects. Subjects were unaware of any sleep disturbance due to the drug although the electroencephalogram (EEG) showed increased wakefulness. The onset of rapid-eye-movement (REM) sleep was delayed and the total amount reduced; the amount of stage 2 sleep was increased. The only effect of the drug on mood was to decrease the level of alertness prior to sleep. There was a slight but significant increase in the pre-sleep systolic blood pressure. There were no effects due to drug withdrawal.
TL;DR: Platelet monoamine oxidase activity is significantly lower in chronic schizophrenic patients with a family history of schizophrenia compared to schizophrenics with no affected relatives and normal controls, suggesting that the lack of uniformity across previous MAO studies of schizophrenia may be explained by the presence of biochemically normal phenocopies.
Abstract: Platelet monoamine oxidase (MAO) activity is significantly lower in chronic schizophrenic patients with a family history of schizophrenia compared to schizophrenics with no affected relatives and normal controls. These results are consistent with the concept of genetic and biologic heterogeneity in schizophrenia and suggest that the lack of uniformity across previous MAO studies of schizophrenia may be explained in part by the presence of biochemically normal phenocopies.
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TL;DR: A role for prostaglandins in the regulation of pineal function is suggested andIndomethacin treatment of rats resulted in a significant increase in pineal monoamine oxidase type A activity, whereas it depressed MAO type B and hydroxyindole-O-methyl transferase activities.
Abstract: Indomethacin treatment of rats resulted in a significant increase of pineal monoamine oxidase (MAO) type A activity, whereas it depressed MAO type B and hydroxyindole-O-methyl transferase activities. Indomethacin also significantly impaired the nocturnal rise of pineal serotonin-N-acetyltransferase activity and melatonin content. These results suggest a role for prostaglandins in the regulation of pineal function.
TL;DR: The results show a large increase in MAO A activity in the endometrial gland cells in the secretory phase of the menstrual cycle and monoamine oxidase B activity was found in both endometrium and myometrium but did not show a cyclical variation in activity.
Abstract: The enzymes monoamine oxidase A (MAO A), monoamine oxidase B (MAO B) and benzylamine oxidase (BzAO) have been localized histochemically in the human uterus during various phases of the menstrual cycle. The results show a large increase in MAO A activity in the endometrial gland cells in the secretory phase of the cycle. MAO B activity was found in both endometrium and myometrium but did not show a cyclical variation in activity. BzAO was localized primarily in the tunica media of the myometrial blood vessels. These observations have been supported by parallel biochemical assays.
TL;DR: While genetics may be the major determinant of monoamine oxidase (MAO) activity, many hormonal, dietary, and even immunological factors may also be important and helpful in understanding individual variation in MAO levels.
Abstract: While genetics may be the major determinant of monoamine oxidase (MAO) activity, many hormonal, dietary, and even immunological factors may also be important. Knowledge of these factors may be helpful not only in understanding individual variation in MAO levels, but in the application of platelet MAO activity as a clinical laboratory aid.
TL;DR: Only by understanding the genetic and environmental factors controlling levels of A and B types of MAO activity can the authors hope to evaluate and manipulate the role ofMAO in human neurophysiology.
Abstract: In establishing the role of inherited variations in levels of monoamine oxidase (MAO) activity in neuropsychiatric diseases, it is important to measure levels of both A and B types of activity as they appear to be under separate genetic control. Levels of A and B types of activity can be evaluated in fibroblasts and platelets, respectively. A number of genes could be involved in determining levels of activity, including those coding for the catalytic and noncatalytic subunits of the enzyme, as well as those coding for enzymes involved in covalent attachment of the flavin cofactor, other processing steps, degradation of MAO, and lipid metabolism. Different genes may be critical in controlling activity levels in various cell types depending on differential expression of the genome. In order to establish the molecular basis of variation in activity, techniques should be employed to assess the structure and conformation of the enzyme, as well as the number of enzyme molecules and their interaction with other cellular components. Only by understanding the genetic and environmental factors controlling levels of A and B types of MAO activity can we hope to evaluate and manipulate the role of MAO in human neurophysiology.
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TL;DR: No significant difference between schizophrenic patients and normal controls was found although in both groups chronic undifferentiated schizophrenics with paranoid features had a trend towards lower DBH activity than the other patients and controls.
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TL;DR: The interaction of the substrate-selective irreversible inhibitor J-508 with the B form of human brain monoamine oxidase has been investigated, and the conditions necessary for this inhibitor to “titrate” the concentration of this enzyme form determined.
Abstract: The interaction of the substrate-selective irreversible inhibitor J-508 [N-methyl-N-propargyl-(1-indanyl)-ammonium hydrochloride] with the B form of human brain monoamine oxidase has been investigated, and the conditions necessary for this inhibitor to “titrate” the concentration of this enzyme form determined. It was found that the concentration of monoamine oxidase-B determined in this way was the same when either benzylamine or β-phenethylamine was used to assay for activity, which would indicate that this enzyme form is not heterogeneous. Furthermore, the variation in activity from sample to sample was found to be due to a variation in the concentration of available monoamine oxidase-B active centers, rather than due to a variation in the molecular turnover numbers of this enzyme form towards its amine substrates.
TL;DR: Because of this property, J-508 could be used, under the appropriate conditions, to ‘titrate’ the concentration of MAO-B active centres in the human platelet, although some non-specific binding of this compound to sites other than the active centre of this enzyme form was found, thus limiting the accuracy of the titration method.
Abstract: The monoamine oxidase B (MAO-B) selective inhibitor J-508 (N-methyl-N-propargyl-(1-indanyl)-ammonium chloride) appears to interact with MAO-B in a manner consistent with a ‘suicide’ reaction. Because of this property, J-508 could be used, under the appropriate conditions, to ‘titrate’ the concentration of MAO-B active centres in the human platelet, although some non-specific binding of this compound to sites other than the active centre of this enzyme form was found, thus limiting the accuracy of the titration method. The molecular characteristics of human platelet MAO-B (Km, Vmax, approximate enzyme concentrations and molecular turnover numbers) towards three of its monoamine substrates have been estimated. The natural variation of platelet MAO-B activity from individual to individual is due to a variation in the Vmax without a variation in the Km towards benzylamine as substrate, and is based, at least in part, upon a variation in the concentration of this enzyme form.