Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOAMINE OXIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,207 records · Page 67Linked to original sources
PubMed2004

An association between a functional polymorphism in the monoamine oxidase a gene promoter, impulsive traits and early abuse experiences.

Monoamine oxidase A (MAOA) activity is altered in mood disorders and lower activity associated with aggressive behavior. The gene has a functional polymorphism with a variable number tandem repeat (VNTR) in the upstream regulatory region (MAOA-uVNTR). In this study, we examined possible associations between the MAOA-uVNTR polymorphism and mood disorders, suicidal behavior, aggression/impulsivity, and effects of reported childhood abuse. In total, 663 unrelated subjects with a psychiatric disorder and 104 healthy volunteers were genotyped for the 30 base pair functional VNTR. A novel repeat variation was identified. No statistically significant associations were found between this functional MAOA-uVNTR polymorphism and mood disorders or suicide attempts. However, the lower expression allele was associated with a history of abuse before 15 years of age in male subjects and with higher impulsivity in males but not females. Our results suggest that the lower expression of the MAOA-uVNTR polymorphism is related to a history of early abuse and may sensitize males, but not females, to the effects of early abuse experiences on impulsive traits in adulthood. The polymorphism may be a marker for impulsivity that in turn may contribute to the risk for abuse. This trait could then be further aggravated by abuse.

Adult↗
PubMed1979

Brain region differences and some characteristics of monoamine oxidase type A and B activities in the vervet monkey.

Monoamine oxidase in the vervet monkey showed greater variations in activity in six brain regions when tyramine or phenylethylamine was used as the substrate (3.8- to 4.1-fold differences) than when serotonin was the substrate (1.8-fold differences). With phenylethylamine and tyramine as substrates, the highest MAO specific activities were found in the hypothalamus and the lowest in the cerebellum and cortex. With serotonin as the substrate, the highest specific activities were in the mesencephalon and cortex. The inhibition of tyramine deamination by clorgyline and deprenyl yielded biphasic plots indicative of the presence of MAO-A and MAO-B enzyme forms in the vervet brain. On the basis of these inhibitor curves, the vervet brain could be estimated to contain approximately 85% MAO-B and 15% MAO-A, in contrast to rat brain which contains 45% MAO-B and 5% MAO-A. The inhibition of serotonin deamination by deprenyl in vervet brain yielded a biphasic plot, suggesting that some serotonin deamination in the vervet is accomplished by the MAO-B enzyme form. Estimations of the relative amounts of MAO-A and MAO-B based on inhibitor curves or based on substrate ratios yielded proportionate results which were in close agreement across the different brain regions, supporting the validity of these approaches to estimating MAO-A and MAO-B activities.

Animals↗
PubMed1996

Morphologic analysis of rat retino-collicular neuron terminals containing monoamine oxidase.

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional reconstruction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.

Animals↗
PubMed1975

Extraneuronal monoamine oxidase in rat heart: biochemical characterization and electron microscopic localization.

Monoamine oxidase (MAO) increases in an age-weight relationship in the hearts of male rats. Accumulation of MAO is not related to the activities of such mitochondrial enzymes as succinic dehydrogenase or cytochrome oxidase which do not change with age. Our previous experiments, utilizing serotonin as a substrate, have determined that cardiac MAO in the young rat does not change after chemical sympathetectomy with 6-hydroxydopamine. In this study, rats of different ages were treated with 6-hydroxy-dopamine to investigate the neuronal vs. non-neuronal distribution of MAO in the heart. After sympathetectomy, various parts of the hearts and fractions of the hearts isolated by differential centrifugation were tested for changes in MAO activity with two different substrates (kynuramine and 14C-tryptamine). It was not possible to detect any changes in MAO activity in any parts or subcellular fractions of the heart as a result of denervation. Studies with clorgyline, the MAO inhibitor, in control and sympathetecomized animals revealed that rat cardiac MAO is mostly of the type A enzyme, which was originally thought to be neuronal. A histochemical technique for the electron microscopic demonstration of MAO with osmiophilic thiocarbamyl nitro blue tetrazolium was used in the rat heart in order to determine the ultrastructural location of the enzyme. Histochemical localization of MAO with the electron microscope using tryptamine as the substrate indicates that a substantial portion of rat cardiac MAO is located near the outer membranes of mitochondria within myocardial cells. This histochemical technique provides no evidence to support differential centrifugation data which suggests the presence of a sarcoplasmic reticular (microsomal) MAO in rat heart.

Aging↗
PubMed1993

Characterisation of wild-type and mutant forms of human monoamine oxidase A and B expressed in a mammalian cell line.

Monoamine oxidase (MAO)-A and MAO-B are FAD-containing mitochondrial enzymes which catabolize biogenic and xenobiotic amines. The N-terminal regions of both forms of MAO contain an ADP-binding consensus sequence found in several dinucleotide-dependent enzymes, but otherwise show remarkable sequence differences. In order to investigate whether the N-terminal region of MAOs participates in the different catalytic properties and inhibitor specificities exhibited by MAO-A and MAO-B, we constructed chimeric A/B forms and expressed them in a human embryonic kidney cell line (293 cells). The MAO-A chimeric form containing the N-terminus (36 amino acids) of MAO-B and the B chimera having the first 45 amino acid sequence of MAO-A were both catalytically active. Compared to the respective wild-type form, they did not show any significant difference in their catalytic properties (Km, kcat) towards the substrates tested or in their sensitivity towards inhibitors. This indicates that the N-terminal region of the two isoenzymes is not involved in the different specificities of MAO-A and MAO-B. Substitution of Cys-397 of MAO-B, i.e. the residue covalently anchoring FAD, with an Ala or a His residue resulted in the total loss of enzymatic activity, suggesting that the covalent coupling of FAD to MAO occurs specifically at the-SH group of cysteine.

Cells, Cultured↗
PubMed2006

Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis.

The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-dependent cardiomyocyte apoptosis. In H9c2 cardiomyoblasts, MAO-A-dependent reactive oxygen species generation led to mitochondria-mediated apoptosis, along with sphingosine kinase-1 (SphK1) inhibition. These phenomena were associated with generation of proapoptotic ceramide and decrease in prosurvival sphingosine 1-phosphate. These events were mimicked by inhibition of SphK1 with either pharmacological inhibitor or small interfering RNA, as well as by extracellular addition of C(2)-ceramide or H(2)O(2). In contrast, enforced expression of SphK1 protected H9c2 cells from serotonin- or H(2)O(2)-induced apoptosis. Analysis of cardiac tissues from wild-type mice subjected to ischemia/reperfusion revealed significant upregulation of ceramide and inhibition of SphK1. It is noteworthy that SphK1 inhibition, ceramide accumulation, and concomitantly infarct size and cardiomyocyte apoptosis were significantly decreased in MAO-A-deficient animals. In conclusion, we show for the first time that the upregulation of ceramide/sphingosine 1-phosphate ratio is a critical event in MAO-A-mediated cardiac cell apoptosis. In addition, we provide the first evidence linking generation of reactive oxygen species with SphK1 inhibition. Finally, we propose sphingolipid metabolites as key mediators of postischemic/reperfusion cardiac injury.

Animals↗
PubMed1993

Changes in monoamine levels in mouse brain elicited by forced-swimming stress, and the protective effect of a new monoamine oxidase inhibitor, RS-8359.

As a stress model, a forced swimming test was applied to mice; and a typical behavioral change, an immobile posture, was recognized. This affected the brain monoamine levels significantly. The norepinephrine concentration was reduced, while that of its product was increased; and in the case of dopamine, both the amount of the amine and its product were increased. Stress increased the levels of serotonin and its product in the brain. The effects of RS-8359, (+/-)-4-(4-cyanophenyl)amino-6,7-dihydro-7-hydroxy-5H-cyclopenta[d ]- pyrimidine, a new inhibitor of type A monoamine oxidase, on the behavioral and biochemical changes caused by forced swimming were also investigated. RS-8359 significantly improved the immobile posture elicited by the forced swimming test. It reduced the increased turnover of norepinephrine and serotonin systems caused by swimming. These results suggest that the effect of RS-8359 on behavioral and biochemical changes by stress may be mainly due to its effects on norepinephrine and serotonin systems, presumably by the inhibition of type A monoamine oxidase.

Animals↗
PubMedDate not supplied

[Possible change in the substrate specificity of the monoamine oxidase of rat brain and liver mitochondria in hyperoxia].

Maintenance of animals in conditions of increased oxygen pressure at 4 atm within 1 h caused a decrease in activity of monoamine oxidase from rat brain mitochondria and liver tissue; at the same time, deamination of putrescine and AMP was increased. Deamination of glucosamine was also observed in brain mitochondria. The qualitative alterations in the monoamine oxidase activity were more distinct in brain than in liver tissue. The enzymatic activity was partially restored by addition of ascorbic acid to the suspension of mitchondria.

Adenosine Monophosphate↗
PubMed2001

Regional serotonin metabolism in the brain of transgenic mice lacking monoamine oxidase A.

The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and on the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5-HT and a lower level of its metabolite, 5-HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5-HIAA/5-HT ratio in various brain regions differed considerably, the decrease of the 5-HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41-45% of control values), with the exception of the frontal cortex, where the decrease of the 5-HIAA/5-HT was somewhat smaller (to 54%). The presence of the remaining 45% +/- 1.9% of the control ratio value indicates rather effective oxidative deamination of 5-HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5-HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures.

Amygdala↗
PubMed2003

Monoamine oxidase A imaging in peripheral organs in healthy human subjects.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of many biogenic and dietary amines. Though studies of MAO have focused mainly on its regulatory role in the brain, MAO in peripheral organs also represents a vast mechanism for detoxifying vasoactive compounds as well as for terminating the action of physiologically active amines, which can cross the blood brain barrier. Indeed, robust central and peripheral MAO activity is a major requirement in the safe use of many CNS drugs, particularly antidepressants, and thus an awareness of the MAO inhibitory potential of drugs is essential in therapeutics. In this study, we examined the feasibility of quantifying MAO A in peripheral organs in healthy human subjects using comparative positron emission tomography (PET) imaging with carbon-11 (t(1/2): 20.4 min) labeled clorgyline ([(11)C]clorgyline) a suicide inactivator of MAO A and its deuterium labeled counterpart ([(11)C]clorgyline-D2). Heart, lungs, kidneys, thyroid, and spleen showed a robust deuterium isotope effect characteristic of MAO and the magnitude of the effect was similar to that of trancylcypromine, an irreversible MAO inhibitor used in the treatment of depression. Liver time-activity curves were not affected by deuterium substitution precluding the estimation of liver MAO in vivo. In organs showing an isotope effect, MAO A is greatest in the lungs and kidneys followed by the thyroid and heart. This method, which has been previously applied in the human brain, opens the possibility to also directly assess the effects of different variables including smoking, dietary substances, drugs, disease, and genetics on peripheral MAO A in humans.

Adult↗
PubMed1993

Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.

Animals↗
PubMed1984

MDL 72145, an enzyme-activated irreversible inhibitor with selectivity for monoamine oxidase type B.

MDL 72145, (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine hydrochloride, was designed and synthesised as a potential enzyme-activated irreversible inhibitor of monoamine oxidase (MAO). In vitro, the compound displayed time-dependent pseudo-first-order irreversible inhibitory characteristics with high selectivity for the B form of rat brain mitochondrial MAO. At 10 degrees C the Ki and tau 50 values for the B enzyme were 40 microM and 1.7 min, respectively, while these same kinetic constants for the A enzyme were 131 microM and 14.5 min, respectively. Selective protection against inactivation of the two forms of MAO by MDL 72145 was obtained by preincubating the enzyme with suitable concentrations of the selective A and B substrates, 5-hydroxytryptamine and benzylamine.

Allylamine↗
PubMed2003

Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B.

N-Benzyl- and N-propargyl-1H-pyrrole-2-carboxyamides and some related methylenamines were synthesized and tested for their monoamine oxidase types A and B inhibitory activity. 2-(N-Methyl-N-propargylaminomethyl)-1H-pyrrole (24) was the most potent MAO-A inhibitor of the series [K(i)(MAO-A) = 0.0054 microM], but it was not selective. Inhibitors N-4-fluorobenzyl-1H-pyrrole-2-carboxamide (12) and N-cyclohexylmethyl-1H-pyrrole-2-carboxamide (25) showed the highest MAO-A selectivity indexes (SI) corresponding to 2025 and >2500, respectively, while 2-(N-methyl-N-benzylaminomethyl)-1H-pyrrole (21) was the most selective MAO-B inhibitor, having an SI of 0.0057.

Alkynes↗
PubMed1985

Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy.

Fourteen boys (mean age, 9.2 +/- 1.5 years) with Attention Deficit Disorder (ADD) With Hyperactivity were treated with dextroamphetamine sulfate or a monoamine oxidase inhibitor (MAOI) (six received clorgyline, eight received tranylcypromine sulfate) for four weeks each in a double-blind, cross-over study that included a two-week placebo washout between active drug periods. The MAOIs had immediate, clinically significant benefit and were clinically indistinguishable from dextroamphetamine. Most children responded to both stimulant and MAOI. These findings of equivalent efficacy of MAOIs in ADD are in contrast to our previous studies with neurotransmitter system selective agents, which showed only weak effects, and suggest that multiple neurotransmitter alterations may be required for stimulant drug effects in ADD. The immediate response to MAOIs indicates a different mechanism from that mediating antidepressant effect. The MAOIs may be useful alternate treatments in selected cases of ADD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1986

1-Phenylcyclobutylamine, the first in a new class of monoamine oxidase inactivators. Further evidence for a radical intermediate.

1-Phenylcyclobutylamine (PCBA) is shown to be both a substrate and a time-dependent irreversible inactivator of monoamine oxidase (MAO). Inactivation results in attachment to the flavin cofactor. For every molecule of PCBA leading to inactivation, 325 molecules are converted to product. The first metabolite formed is identified as 2-phenyl-1-pyrroline; then after a lag time, 3-benzoylpropanal and 3-benzoylpropionic acid are generated. The 3-benzoylpropanal is a product of MAO-catalyzed oxidation of 2-phenyl-1-pyrroline (presumably, of its hydrolysis product, gamma-aminobutyrophenone). The aldehyde is nonenzymatically oxidized by nascent hydrogen peroxide to the carboxylic acid. These results are consistent with a one-electron oxidation of PCBA to the amine radical cation followed by homolytic cyclobutane ring cleavage. The resulting radical can partition between cyclization (an intramolecular radical trap) to the 2-phenylpyrrolinyl radical and attachment to the flavin. The cyclic radical can be further oxidized by one electron to 2-phenyl-1-pyrroline. PCBA represents the first in the cyclobutylamine class of MAO inactivators and strongly supports involvement of a radical mechanism for MAO-catalyzed amine oxidations.

Cyclobutanes↗
PubMed1975

Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion.

Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3, 4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35 +/- 8.7 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.

5-Hydroxytryptophan↗
PubMed2000

In vitro inhibition of rat monoamine oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis.

AIM: To study the inhibition of liquiritigenin (1) and isoliquiritigenin (2) isolated from Sinofranchetia chinensis on rat monoamine oxidase A and B (MAO A and B). METHODS: Rat brain mitochondrial fraction, prepared by differential centrifugation, was utilized as a source of MAO activity. MAO activity was determined radiochemically with [14C]5-hydroxytryptamine (5-HT) and [14C]beta-phenylethylamine (beta-PEA) used as MAO A or B specific radiolabled substrates, respectively. The Ki and KI values were obtained from Lineweaver-Burk plot using linear regression analysis. RESULTS: Liquiritigenin and isoliquiritigenin were found to be inhibitory against both MAO A and B in a dose-dependent manner. IC50 (95% of confidence limits) of liquiritigenin and isoliquiritigenin were 32 (26-36) and 13.9 (12.8-15.6) mumol/L for the inhibition of MAO A, and 104.6 (89.0-118.9) and 47.2 (39.5-54.5) mumol/L for that of MAO B, respectively. Lineweaver-Burk transformation of the MAO A inhibition data indicated that the inhibition was non-competitive for both liquiritigenin and isoliquiritigenin whereas their inhibition of MAO B was of mixed type. Regarding MAO A inhibition, the Ki values of liquiritigenin and isoliquiritigenin were 31.5 mumol/L and 14.3 mumol/L, respectively. As to the inhibition of MAO B, the Ki and KI data for liquiritigenin were 164.7 and 15.2 mumol/L, and those for isoliquiritigenin were 62.2 and 9.3 mumol/L, respectively. CONCLUSION: Liquiritigenin and isoliquiritigen inhibited the activity of MAO A and B in rat brain mitochondria, and the latter was more active than the former.

Animals↗