Showing papers on "Monoamine oxidase B published in 1990"

Tissue distribution of human monoamine oxidase A and B mRNA.

Abstract: Monoamine oxidase (MAO) A and B play important roles in the metabolism of biogenic amines. Northern analysis using 32P-labeled subfragments of human liver MAO A and B cDNA clones detected a 5- and a 3-kb transcript, respectively, in most human tissues examined. However, fetal heart and thymus express minute amounts of MAO A transcript, whereas fetal brain, muscle, thymus, spleen, meninges, and placenta express minute amounts of MAO B transcript. Small intestine and placenta express, in addition to the MAO A 5-kb transcript, a 2-kb transcript, which may arise from an alternative polyadenylation site. MAO A and B transcripts are expressed in similar regions of adult human brain. The highest concentrations of these transcripts were located in frontal cortex and locus coeruleus. This study demonstrates the tissue-specific distribution of the MAO genes and will provide insight into the physiological functions of MAO A and B.

Oxidative stress: a role in the pathogenesis of Parkinson's disease.

Abstract: The degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson’s disease (PD) However, the etiology of this degeneration is not known Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN) Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD

Expression of monoamine oxidase B activity in astrocytes of senile plaques.

Abstract: Monoamine oxidase (MAO) histochemistry has been performed in brains from patients with dementia of Alzheimer type (DAT) and aged controls. Conspicuous MAO-positive cell clusters were frequently observed in the amygdala, hippocampus, and insular cortex in the brains of DAT. Double staining with glial fibrillary acidic protein immunohistochemistry revealed that the clusterforming MAO-positive cells were astrocytes. Using Bielschowsky's method, Congo red and thioflavin S counterstaining, this astrocytic mass was shown to be associated with senile plaques. By the enzyme inhibition experiment, MAO activity in senile plaques was revealed to be of type B. The present results clearly indicate that MAO-B activity is expressed in fibrillary astrocytes in or around senile plaques, suggesting that these astrocytes metabolize exogenous amines in senile plaques.

Monoamine oxidase and oxidative stress at dopaminergic synapses

Abstract: Increased oxidation of dopamine by monoamine oxidase (MAO) in the striatum is associated with an oxidant stress, expressed as a rise in the level of oxidized glutathione. Oxidation of glutathione is suppressed by MAO inhibitors, such as deprenyl and clorgyline. These observations relate to Parkinson’s disease and to the clinical trial of deprenyl as an agent that may retard progression of the disease.

Marked Amine and Amine Metabolite Changes in Norrie Disease Patients with an X‐Chromosomal Deletion Affecting Monoamine Oxidase

Abstract: Urinary and plasma amines and amine metabolites were quantified in two individuals with Norrie disease resulting from a deletion in chromosomal region Xp11.3, recently reported to be associated with absence of the gene encoding monoamine oxidase (MAO)-A and nondetectable MAO-A activity in fibroblasts and MAO-B activity in platelets. Marked (four-to 100-fold) elevations in levels of urinary phenylethylamine, o-tyramine, and m-tyramine (which are preferential substrates for MAO-B) and marked reductions (90%) in levels of 3-methoxy-4-hydroxyphenylglycol (a deaminated metabolite of norepinephrine, a preferential substrate for MAO-A) in urine and plasma confirmed the presence of a systemic, functionally significant reduction in the activities of both MAO isozymes. The magnitude of these changes, which are equivalent to those found in subjects taking MAO-inhibiting antidepressants, suggests that early initiation of dietary and drug restrictions may be clinically important in these and other patients with X-chromosomal mutations involving MAO. These findings further support the proposition that the MAOA and MAOB genes are located in close proximity on the X chromosome. Negligible changes in the metabolites of dopamine and serotonin raise the possibility that other metabolic pathways are of importance for their production, that dietary or intestinal bacterial sources contribute substantially to the presence of these amine metabolites in urine, or both.

Primary structure of rat monoamine oxidase A deduced from cDNA and its expression in rat tissues.

Abstract: The cDNA for rat monoamine oxidase A (MAO-A) mRNA was isolated from a liver cDNA library in λ gt11 as the cDNA species cross-hybridizing with rat monoamine oxidase B (MAO-B) cDNA. The primary structure of the protein, deduced from the nucleotide sequence, consisted of 526 amino acid residues and its molecular mass was calculated to be 59.6 kD. The amino acid sequence shows about 70% identity with that of rat MAO-B. Northern blot analysis showed that MAO-A mRNA was expressed in various rat tissues and the highest expression was observed in heart. The MAO-B mRNA was quite different from MAO-A mRNA in the tissue-specific expression and liver had the highest level of the mRNA.

The role of monoamine oxidase, iron-melanin interaction, and intracellular calcium in Parkinson's disease.

Abstract: Recent evidence suggests that iron accumulates in substantia nigra pars compacta of patients with Parkinson’s disease (PD). This finding is compatible with changes in the respiratory chain activity, increase of malondialdehyde concentration (a measure of lipid peroxidation), decrease of enzyme activity of enzymes involved in detoxication of hydrogen peroxide and oxygen radical species, increased MAO-B-activity in this brain area etc. All these data suggest that oxidative stress may play a certain role in the pathobiochemistry of PD. In addition to the description of the neuroprotective mechanism of the MAO-B-inhibitor L-deprenyl a new aspect focuses the role of the endogenous MAO-B substrates “polyamines” which occur both in neurons and glia. A further aspect of this review deals with the role of calcium as cellular toxin. Although of major importance it is not decided yet whether these biochemical changes are of primary or secondary importance to the pathogenesis of PD.

Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethyl-selegiline in the rat

Abstract: The monoamine oxidase (MAO) B activity of rat brain was inhibited by selegiline and its desmethyl-metabolite in vitro with IC50-values of 11.25 nmol/1 and 625.00 nmol/1, respectively. When measured in an ex vivo experiment following oral treatment of rats, the large difference in potency was distinctly reduced, from factor 60 in vitro to factor 3 ex vivo. Restoration experiments of MAO-B-activity after cessation of treatment revealed a nearly identical time course for both compounds. It is concluded that desmethyl-selegiline is an irreversible blocker of MAO-B, nearly equipotent to selegiline after multiple oral administration. No pharmacologically relevant inhibition of MAO-A was found with both compounds.

Some basic aspects of reversible inhibitors of monoamine oxidase-A.

Abstract: A novel class of antidepressants is emerging with considerable therapeutic potential: reversible inhibitors of monoamine oxidase type A (RIMA). Moclobemide (Aurorix®) is a representative RIMA. It is a fully and rapidly reversible inhibitor of MAO-A with a correspondingly intermediate duration of action in vivo. It is free of hepatotoxicity and produces a much weaker potentiation of the tyramine pressor effect than the classical irreversible MAO inhibitors. Interaction of MAO inhibitors and monoamine reuptake inhibitors with tyramine is discussed on the basis of experiments in conscious rats. The issue of tyramine content of foods and beverages has been reinvestigated and its relevance for treatment with RIMA antidepressants is discussed. Recently observed antihypoxic (neuroprotective) effects of moclobemide suggest new indications for this compound.

Monoamine Oxidase and Dementia: Treatment with an Inhibitor of MAO-B Activity

Abstract: Patients suffering from Alzheimer type dementia have demonstrated an increase in MAO-B activity. Treatment of these patients with an inhibitor of the monoamine oxidase activity, such as L-Deprenyl (LD), might therefore provide a valid therapeutic intervention. The efficacy of LD was examined in a double-blind, drug versus placebo (PL) study on 20 patients diagnosed between stages 3 and 5 of primary degenerative dementia. Treatment duration was 90 days (5 mg twice a day). All patients underwent clinical, behavioral, and memory evaluations every 30 days. Subjects in the LD group demonstrated an improvement on both attention and memory measures; some of the changes were apparent after only 30 days of treatment. PL patients showed no such improvement and also evidenced a decrease in behavior efficiency during the experimental period. Two patients dropped out of the study, 1 from each treatment group. No differences were found in either the type and number of concomitant treatments or side effects between groups.

Phenylethylamine in the CNS: effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission.

Abstract: Phenylethylamine is present in brain in tiny quantities, it is heter-ogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly. If deuterium is substituted for hydrogen on the α carbon of the side chain then it exhibits profound isotope effects to MAO and its penetration and persistence in the brain is considerably enhanced. In the presence of MAO-B inhibitors treatment with reserpine causes reciprocal changes to PE and DA suggesting a functional relationship between them and after unilateral lesions of the substantia nigra an ipsilateral reduction in striatal PE is seen suggesting again a co-relationship with DA. Following iontophoresis PE has been shown to exhibit indirect sympathomimetic effects but in addition when applied at low currents concurrently with DA or NA it causes post synaptically a substantial potentiation in the actions of the latter amines. As a result of this and other data PE has been proposed to be a neuromodulator of catecholaminergic transmission.

Monoamine oxidase inhibitors in depression: history and mythology.

Abstract: On 6 September 1944, the Second World War entered a new phase when the Germans unveiled their secret weapon. They started to bombard southern England with V2 rockets, to great consternation and loss of life. About 1000 were used, and 3000 more in Europe, all powered by ethanol and liquid oxygen. Even so, there were difficulties in the liquid oxygen production line and the German war machine started to turn to other

Platelet monoamine oxidase B activity in parkinsonian patients.

Abstract: Monoamine oxidase B (MAO B) plays a pivotal role in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism. An increased MAO B activity in platelets of patients with idiopathic Parkinson's disease (PD) is reported in this study. The possibility that high MAO B activity may represent a trait of vulnerability for PD by enhancing the neurotoxic effects of environmental compounds is discussed.

Immunofluorescence cytochemistry on thin frozen sections of human substantia nigra for staining of monoamine oxidase A and monoamine oxidase B: a pilot study.

Abstract: Immunofluorescence cytochemistry on thin frozen sections of human substantia nigra for staining of MAO-A and MAO-B revealed that only about 10% of the melanin-containing neurons are positive for MAO-A, while they are substantially free of MAO-B.

Turnover of monoamine oxidase B (MAO-B) in pig brain by positron emission tomography using 11C-L-deprenyl.

Abstract: Positron emission tomography (PET) was applied to investigate the rate of turnover of pig brain MAO-B. For this purpose 11 C-L-deprenyl was used as an irreversible ligand, which bind stoichiometrically to the enzyme. A tracer dose of11 C-L-deprenyl was injected and PET scans performed to obtain baseline deprenyl binding. A high dose of unlabelled deprenyl was then administered to inhibit the enzyme and tracer doses of 11 C-L-deprenyl, with subsequent PET analyses, were given at 0, 2, 7, 21 and 42 days. The half-life for the turnover rate calculated was found to be 6.5 days.

Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines.

Abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its primary oxidation product, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), are mechanism-based inhibitors of monoamine oxidases A and B. The pseudo-first-order rate constants for inactivation were determined for various analogues of MPTP and MPDP+ and the concentrations in all redox states were measured throughout the reaction. Disproportionation was observed for all the dihydropyridiniums, but non-enzymic oxidation was insignificant. The dihydropyridiniums were poor substrates for monoamine oxidase A and, consequently, inactivated the enzyme only slowly, despite partition coefficients lower than those for the tetrahydropyridines. For monoamine oxidase B, the dihydropyridiniums were more effective inactivators than the tetrahydropyridines. Substitutions in the aromatic ring had no major effect on the inactivation of monoamine oxidase B, but the 2'-ethyl- and 3'-chloro-substituted compounds were very poor mechanism-based inactivators of monoamine oxidase A. It is clear that both oxidation steps can generate the reactive species responsible for inactivation.