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Localization of monoamine oxidase A and B mRNA in the rat brain by in situ hybridization.

Monoamine oxidases A and B (MAOA and MAOB) are the major catabolic isoenzymes of catecholamines and serotonin in the mammalian brain. Although the distribution of the monoamine oxidase protein has been mapped by ligand binding and immunohistochemistry, the sites of MAOA and MAOB synthesis have not been precisely determined. In this study, we used in situ hybridization to visualize MAOA and MAOB mRNA in the rat brain by using specific cDNA and oligonucleotide probes. MAOA mRNA was localized in major monoaminergic cell groups, such as the dorsal vagal complex, the C1/A1 groups, the locus ceruleus, the raphe nuclei, the substantia nigra, and the ventral tegmental area. MAOA mRNA was also found in forebrain structures, such as the cortex, the hippocampus, the thalamus, and the hypothalamus. In contrast to the distribution of MAOA mRNA, high levels of MAOB mRNA were present in only three brain regions: the area postrema, the subfornical organ, and the dorsal raphe. The in situ visualization of MAO mRNA demonstrates that MAOA mRNA synthesis is wide spread in many catecholaminergic and serotonergic cell groups, whereas MAOB mRNA synthesis is far more discrete and limited. The different expression patterns of MAOA and MAOB suggests that may also have different physiological functions.

Animals↗

Monoamine oxidase inhibitors: a review.

Current knowledge about monoamine oxidase (MAO) inhibitors is reviewed, with particular attention to the mode of action, prognostic indicators, treatment protocol, response prediction, toxicity, and untoward drug interactions. The MAO inhibitors are often effective in the treatment of affective disorders, anxiety states, and phobias.

Antidepressive Agents, Tricyclic↗

Inhibition of brain monoamine oxidase activity by the generation of hydroxyl radicals: potential implications in relation to oxidative stress.

Monoamine oxidase (MAO) is an enzyme involved in brain catabolism of monoamine neurotransmitters whose oxidative deamination results in the production of hydrogen peroxide. It has been documented that hydrogen peroxide derived from MAO activity represents a special source of oxidative stress in the brain. In this study we investigated the potential effects of the production of hydroxyl radicals (*OH) on MAO-A and MAO-B activities using mitochondrial preparations obtained from rat brain. Ascorbic acid (100 microM) and Fe2+ (0.2, 0.4, 0.8, and 1.6 microM) were used to induce the production of *OH. Results showed that the generation of *OH significantly reduced both MAO-A (85-53%) and MAO-B (77-39%) activities, exhibiting a linear correlation between both MAO-A and MAO-B activities and the amount of *OH produced. The reported inhibition was found to be irreversible for both MAO-A and MAO-B. Assuming the proven contribution of MAO activity to brain oxidative stress, this inhibition appears to reduce this contribution when an overproduction of *OH occurs.

Animals↗

Inhibition by Zn(2+) of A-form monoamine oxidase in monkey brain mitochondria.

The effects of ZnSO(4) on mitochondrial monoamine oxidase (MAO) activity in monkey brain were compared with those in rat and rabbit, in vitro. After preincubation at 25 degrees C for 20 min with 1 microM ZnSO(4), MAO-A activity in monkey brain was about 50% using serotonin (5-HT) as a substrate, and the inhibition was proportional to the concentration of ZnSO(4). However, ZnSO(4) had no effect on MAO-B activity in monkey brain using beta-phenylethylamine (beta-PEA) as a substrate. The inhibition by ZnSO(4) of MAO-A activity was competitive and reversible. CdSO(4) also inhibits MAO-A, but not MAO-B in monkey brain mitochondria. ZnSO(4) did not inhibit either MAO-A or MAO-B activity in rat and rabbit brain mitochondria. These results indicate that the inhibiting action of Zn(2+) differs depending on animal species. In monkey brain mitochondria, MAO-A was highly sensitive to Zn(2+) and MAO-B was less sensitive. These results also suggest that Zn(2+) may regulate the level of catecholamine content in monkey brain.

Animals↗

Proteases as probes of mitochondrial monoamine oxidase topography in situ.

Selective inactivation of the multiple forms of mitochondrial monoamine oxidase (MAO) by proteases in intact and hypotonically disrupted rat liver mitochondria has been used to examine the question of differential membrane orientations of the A and B enzymes. Proteases used as probes included trypsin, beta-chymotrypsin, and the extracellular protease of Staphylococcus aureus, chosen for their different amino acid specificities. With all three proteases, no changes in the relative rates of MAO-A and MAO-B inactivation were observed after disruption of the mitochondria. Trypsin and beta-chymotrypsin gave much faster rates of MAO-A inactivation in both intact and disrupted mitochondria. The selective effect of trypsin on MAO-A was also confirmed in human placental mitochondria, which possess only A-type activity. The effectiveness of hypotonicity in disrupting the outer membrane of the mitochondria was shown by rapid protease inactivation of an intermembrane space marker enzyme, adenylate kinase (EC 2.7.4.3). Contrary to some recent reports in the literature, these findings strongly suggest that the MAO-A and MAO-B multiple-form catalytic activities do not reside on opposite faces of the membrane.

Animals↗

Pharmacology and physiology of monoamine oxidase activity in vertebrates--a comparative study.

Monoamine oxidase (MAO) activity is high in brain, where it regulates neurotransmitter levels, and in the 'detoxifying' organs. Two MAO isoenzymes (A and B) apparently exist in terrestrial tetrapods, but only one form (type A-like) can be detected in teleosts and in aquatic amphibia. MAO activity is regulated by both endogenous (hormones, substrates) and exogenous (daylength, temperature) factors.

Animals↗

Rapid conversion from one monoamine oxidase inhibitor to another.

BACKGROUND: Numerous sources state that switching from one monoamine oxidase (MAO) inhibitor to another can be done only after a 14-day washout period. In hospitalized patients and severely depressed outpatients, such a wait may be impracticable. METHOD: We reviewed the case histories of eight consecutive and random patients whom we converted from one MAO inhibitor to another within less than the recommended waiting period. RESULTS: Only one patient experienced troubling adverse effects, and these effects were brief and time-limited. The patient's symptoms were indicative of either withdrawal from tranylcypromine or a mild serotonin syndrome. All other patients tolerated the conversion well with minimal or no adverse effects. Four of the eight patients eventually responded to the new MAO inhibitor. CONCLUSION: These results suggest that some patients can be cautiously but rapidly switched from one MAO inhibitor to another without prolonged drug-free periods. Unquestionably, this strategy should be used only when the clinical picture mandates a rapid conversion. Further, it should be reserved for those patients with established high compliance and should include close monitoring and the use of a low-tyramine diet. Extreme caution must still be undertaken in utilizing this approach until larger studies more accurately determine the frequency of serious adverse effects.

Adult↗

Monoamine oxidase inhibition during brain development induces pathological aggressive behavior in mice.

BACKGROUND: Monoamine oxidase (MAO) is historically a focus of concern in research on impulsive and aggressive behavior. Recent studies in a single kindred with a point mutation in the MAO-A gene, together with phenotypic evaluations of MAO-A knockout mice, have sharpened this interest. The goal of this study was to investigate the behavioral consequences of MAO inhibition during brain development and to determine the extent to which specific effects could be attributed to MAO- A versus MAO-B. METHODS: MAO-A and B inhibitors were administered, separately or in combination, during gestation and lactation. Behavioral evaluations included neurologic testing, delay of rewarded response, and the resident-intruder aggression paradigm, conducted before and after an acute pharmacologic challenge. RESULTS: Total prenatal MAO inhibition produced a pervasive increase in aggressive behavior, whereas MAO-B inhibited mice demonstrated a similar pattern of lower intensity. Aggression was elevated in MAO-A inhibited mice only after acute pharmacologic challenge, suggesting prenatal sensitization. CONCLUSIONS: Developmental inhibition of MAO activity engenders behavioral effects that parallel those observed in animals with genetic ablation of MAO function. These data underscore the importance of neurochemical changes during development and provide a possible model for disinhibited aggression, common in clinical populations.

Aggression↗

Revised mechanism for inactivation of mitochondrial monoamine oxidase by N-cyclopropylbenzylamine.

A mechanism previously proposed for inactivation of monoamine oxidase (MAO) by N-cyclopropylbenzylamine (N-CBA) [Silverman, R. B., & Hoffman, S. J. (1980) J. Am. Chem. Soc. 102, 884-886] is revised. Inactivation of MAO by N-[1-3H]CBA results in incorporation of about 3 equiv of tritium into the enzyme and release of [3H]acrolein. Treatment of inactivated enzyme with benzylamine, a reactivator for N-CBA-inactivated MAO, releases only 1 equiv of tritium as [3H]acrolein concomitant with reactivation of the enzyme. Even after MAO is inactivated by N-[1-3H]CBA, the reaction continues. At pH 7.2, a linear release of [3H]acrolein is observed for 70 h, which produces 55 equiv of [3H]acrolein while 2.3 equiv of tritium is incorporated into the enzyme. At pH 9, only 3.5 equiv of [3H]acrolein is detected in solution after 96 h, but 40 equiv of tritium is incorporated into the enzyme, presumably as a result of greater ionization of protein nucleophiles at the higher pH. N-[1-3H]Cyclopropyl-alpha-methylbenzylamine (N-C alpha MBA) produces the same adduct as N-CBA but gives only 1-1.35 equiv of tritium bound after inactivation of the enzyme. Denaturation of labeled enzyme results in reoxidation of the flavin without release of tritium, indicating attachment is not to the flavin but rather to an amino acid residue. Enzyme inactivated with N-[1-3H]C alpha MBA is reactivated by benzylamine with the release of 1 equiv of [3H]acrolein, which must have come from an adduct attached to an active site amino acid residue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrolein↗

Platelet monoamine oxidase in women with premenstrual syndrome.

Platelet monoamine oxidase (MAO) and RBC catechol-O-methyltransferase (COMT) were studied in 12 women suffering from premenstrual syndrome. No significant variation of platelet MAO or RBC COMT was found during the menstrual cycle, as opposed to previous studies on normal women and monkeys, which report a significant decline of platelet MAO activity in the 5-day period before menses.

Adult↗

Management of monoamine oxidase inhibitor-associated insomnia with trazodone.

Monoamine oxidase inhibitors (MAOIs) have been reported to cause or exacerbate insomnia, sometimes requiring discontinuation despite adequate therapeutic response. The authors present a series of 13 cases of MAOI-associated insomnia managed with addition of trazodone. Twelve patients (92%) had an initial positive response, with nine (69%) able to continue on the combination of MAOI and trazodone without intolerable side effects.

Adult↗

Monoamine oxidase inhibitors, their structural analogues, and neuroprotection.

Monoamine oxidase (MAO) inhibitors have been used for many years in the treatment of psychiatric and neurological disorders. More recently, some of these drugs and their analogues have been shown to have neuroprotective and neurorescue effects in several models of neurologic insult, including in vitro and in vivo models of cerebral ischemia. This review will discuss current evidence regarding these aspects of l-deprenyl, tranylcypromine, phenelzine, and some structurally related drugs.

Animals↗

[An increase in the radioprotective effect of O-methyltyramine and mezaton by monoamine oxidase inhibitors].

Specific 2-propynylamine inhibitors of monoamine oxidase (MAO) pargyline and especially chlorgyline, a selective inhibitor of MAO A (but not deprenyl, a selective inhibitor of MAO B) increase the radioprotective effect of small doses of O-methyltyramine and phenylephrine and do not change the efficacy of large doses. This is consistent with the receptor theory of the mechanism of protective action of amines.

Animals↗

Platelet monoamine oxidase activity in schizophrenic families - kinetic aspects.

Monoamine oxidase activity (MAO) was determined in platelets in samples from a North-Swedish pedigree with a high frequency of schizophrenia. The MAO assay was performed with phenethylamine as substrate and with two concentrations of oxygen (0.06 and 0.12 mM). A tendency to lowered Vmax and increased apparent Km values was observed among the schizophrenic subjects, although there were no statistically significant differences in apparent Km and Vmax values between schizophrenics and their non-schizophrenic relatives.

Blood Platelets↗

Low platelet monoamine oxidase activity in borderline personality disorder.

Platelet monoamine oxidase (MAO) activity was significantly lower in nonpsychotic, nonorganic, unmedicated male inpatients with DSM-III-R borderline personality disorder (BPD) than in nonpsychiatric controls. Patients with BPD who also met DSM-III-R criteria for antisocial personality disorder had significantly lower MAO activity than those with BPD alone. Low MAO activity in this sample did not appear to be related to the comorbid presence of major depressive disorder or a history of substance abuse.

Adolescent↗

Dopamine induces ERK activation in renal epithelial cells through H2O2 produced by monoamine oxidase.

BACKGROUND: The rat renal proximal tubule cells contain a large amount of monoamine oxidase, which catalyzes the oxidative deamination of catecholamines such as dopamine (DA). The aim of this study is to investigate the potential role of hydrogen peroxide (H2O2) produced by monoamine oxidase (MAO) isoform on regulation of cell signaling and function. METHODS: Primary rat proximal tubular cells, which contain almost exclusively MAO-A, and human embryonic kidney 293 (HEK 293) cells stably transfected with human MAO-B cDNA were treated with DA or tyramine in the presence or the absence of some inhibitors. Then, Shc protein tyrosine phosphorylation and extracellular-regulated kinase (ERK) activation were evaluated by immunoprecipitation/immunoblot analysis and cell proliferation by [3H]thymidine incorporation or cell counting. RESULTS: In rat proximal tubule cells, DA induced tyrosine phosphorylation of Shc, ERK activation, and a significant increase in DNA synthesis. The involvement of MAO-dependent H2O2 generation induced by DA (5 micromol/L) was supported by the demonstration that the DA effects were (1) fully prevented by cell pretreatment with the MAO inhibitor pargyline, the antioxydant N-acetylcysteine (NAC), and the DA uptake inhibitor GBR 12909; (2) not abrogated by the D1 and D2 receptor antagonists; (3) observed in HEK 293 MAO-B cells but not in HEK 293 wild-type cells, which do not express MAO; and (4) similar to those induced by another MAO substrate, tyramine. CONCLUSIONS: Taken together, these results show that in addition to the effects related to receptor stimulation, DA, and probably the other catecholamines, may induce some of its effects through the MAO-dependent H2O2 production.

Adaptor Proteins, Signal Transducing↗

Platelet monoamine oxidase and clinical phenomenology of schizophrenia.

Platelet monoamine oxidase activity (MAO) was determined in 39 unmedicated chronic schizophrenic patients and 88 normal control subjects. Platelet MAO activity did not distinguish paranoid from nonparanoid patients or patients who met Taylor and Abrams criteria for narrowly defined schizophrenia from other schizophrenics. Enzyme activity was not related to either prognostic scores or age at onset of illness. MAO activity was decreased in patients compared to controls, and was lower in males than in females. Our findings indicate that clinical phenomenology, as defined in the present study, is of limited use in identifying biological subtypes of schizophrenia with deviant platelet MAO activity.

Adolescent↗