Imipramine inhibits monoamine oxidase activity in hyperglycemic rat brain

The effect of the chronic treatment of tricyclic antidepressants like Imipramine on the catecholamine metabolism of rat brain, in normal and hyperglycemic conditions was investigated. Imipramine was found to elevate the catecholamine levels in controls, while chronic treatment of hyperglycemic animals with the drug, failed to cause any change other than seen as a result of hyperglycemia. The activities of Monoamine oxidase on the other hand, decreases significantly as a result of the treatment, both in controls and in the hyperglycemic state. The results suggest that the drug apart from acting as an antidepressant, assumes the role of a monoamine oxidase inhibitor under pathological conditions.     

In vitro andin vivo effect of organophosphate pesticides on monoamine oxidase activity in rat brain

The effects of some organophosphate pesticides, e.g. lebaycid, metacid and metasystox on the monoamine oxidase (MAO) activity in rat brain mitochondria have been studied. These pesticides cause significant inhibition of MAO activityin vitro but have negligible effects on its activityin vivo.     

Effect of benzamide derivatives on rat brain monoamine oxidase activity in vitro

The ability of moclobamide and other benzamide derivatives to inhibit the activity of monoamine oxidase in the rat brain was studied. Distinct effects of these compounds on the deamination of serotonin and norepinephrine (MAO-A substrates); 2-phenylethylamine (selective MAO-B substrate); tyramine and dopamine (MAO-A and MAO-B substrates) are shown. It was demonstrated that among all the compounds studied moclobamide appeared to be the most active and selective inhibitor of MAO-A: at a concentration of 100 microM it caused a 100% inhibition of serotonin and norepinephrine deamination, which might be explained by the presence of C1 atom in the para-position of benzene ring in moclobamide molecule. Other benzamide derivatives were less active in inhibiting MAO-A and had but a negligible effect on dopamine- and 2-phenylethylamine deamination.     

Effect of neurocatin on the activity of monoamine oxidase B in rat brain synaptosomes

Neurocatin, a small (about 2,000 Dalton) neuroregulator isolated from mammalian brain, is a powerful effector of monoamine oxidase B in rat brain synaptosomes. Incubation of intact synaptosomes with neurocatin caused an inhibition of the enzyme dependent on the concentration of neurocatin. This inhibition became statistically significant at a neurocatin concentration of 10 ng/200 l and was significant at all higher neurocatin concentrations. At 40 ng/200 l, neurocatin inhibited monoamine oxidase B activity by about 60%. This inhibitory effect was almost completely abolished by breaking the synaptosomal membrane by hypotonic buffer prior to incubation with neurocatin. In addition, incubation of the synaptosomes in calcium free medium almost completely abolished the inhibitory effect of neurocatin on monoamine oxidase B. The inhibition appeared to involve covalent modification of the enzyme mediated by a neurocatin receptor(s). Measurements of the kinetic parameters of the enzyme showed that 20 ng of neurocatin caused a statistically significant decrease in V_max (by 20%) with no significant change in K_M, compared to controls. Inhibition of monoamine oxidase by neurocatin is potentially of great clinical importance because this enzyme plays a major role in catabolism of the biogenic amines and alterations in its activity is believed to contribute to several neurological disorders.     

Influence of age on brain vascular and cardiovascular monoamine oxidase activity in the rat

Monoamine oxidase (MAO) activity in brain microvessels and cardiovascular tissues was examined in rats of different age. MAO activity continued to increase with age in the heart, but in contrast, reached maximum activity in three weeks in the aorta, mesenteric artery and mesenteric vein. Between 7 and 60 weeks, there was a small decline in the MAO activity in the testicular artery. The highest MAO activity was found in the cerebral microvessels and increased with age. The half-life of MAO was estimated in the heart and peripheral blood vessels in young and old animals. The half-life of cardiac MAO was increased with age whereas that of the mesenteric vein, mesenteric artery and aorta remained constant between 7 and 112 weeks. Thus an explanation for this increased cardiac MAO activity in old rats was a reduced rate of degredation of this enzyme. The high activity of the enzyme in the brain microvessels suggests that it may participate in regulating the influx and efflux of monoamines in the central nervous system.     

Effect of adafenoxate on different rat brain structures monoamine oxidase activity in vitro

1. The effect of the nootropic drug adafenoxate on monoamine oxidase (MAO) activity in rat brain cortex, striatum, hypothalamus and hippocampus has been studied using the following substrates: tyramine (total MAO), serotonin (MAO A) and beta-phenylethylamine (MAO B). 2. In a series of increased concentrations (from 5 x 10(-4) up to 1 x 10(-5) M) adafenoxate inhibits total MAO, MAO A and MAO B in the brain structures studied. 3. The adafenoxate IC50 values obtained illustrate its inhibitory properties and its lack of selectivity toward MAO in the brain structures isolated. 4. The results of our research prove the participation of MAO in the mechanisms through which adafenoxate affects the brain monoaminergic systems and realises its central effects.     

Mitochondrial monoamine oxidase activity and serotonin content of rat brain following gamma-irradiation

It is shown that gamma-irradiation of albino rats with a dose of 30 Gy leads to pronounced phase changes in monoaminoxidase activity and serotonin content in rat brain at early times after whole-body exposure. There is a similar direction of changes in the activity of the enzyme and in the content of the substrate adequate to the latter.     

In vitro andin vivo effect of chloropromazine,imipramine and lithium chloride on monoamine oxidase activity in rat brain mitochondria

Chloropromazine (CPZ) and imipramine at a concentration of 1×10^–3 M inhibit rat brain mitochondrial monoamine oxidase activity in vitro by 70 and 55% respectively, while lithium, even at a concentration of 0.05 M, inhibits the activity of this enzyme very negligibly (4%). In vivo, these drugs at a dose level of 56 mg CPZ, 76 mg Jimipramine and 76 mg lithium chloride/Kg body wt., did not cause any observable variation from normal in brain mitochondrial monoamine oxidase activity.To whom correspondence should be addressed.     

Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain

The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 μM calcium disodium edetate (CaNa₂EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa₂EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa₂EDTA was reversible. CaNa₂EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa₂EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa₂EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.     

Multiple catalytic sites of rat brain mitochondrial monoamine oxidase

We compared the inhibitory and catalytic effects of various monoamines on forms A and B of monoamine oxidase (MAO) on mitochondrial preparations from rat brain in mixed substrate experiments. MAO activity was determined by a radioisotopic assay. MAO showed lower K_m values for tryptamine and β-phenylethylamine than for tyramine and serotonin. The K_m values of the untreated preparation for tyramine, tryptamine, and β-phenylethylamine obtained were the same as those of the form B enzyme and the K_m value for serotonin was the same as that of the form A enzyme. Tyramine and tryptamine were competitive inhibitors of serotonin oxidation and β-phenylethylamine did not bind with form A enzyme or inhibit the oxidation of serotonin, while tyramine and tryptamine were competitive inhibitors of β-phenylethylamine oxidation. Although serotonin was not oxidized by form B enzyme, serotonin was a competitive inhibitor of β-phenylethylamine oxidation. It is suggested that rat brain mitochondrial MAO is characterized by two kinds of binding sites.     

Inhibition of rat brainstem monoamine oxidase activity by CGP 6085 A

CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl)piperidine] HCl, a known serotonin inhibitor, also inhibits rat brainstem monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in both in vivo and in vitro experiments. Serotonin (5-HT) deamination by MAO-A is inhibited 35% at a dose of 100 mg/kg i.p. in vivo. Similar experiments show a maximal 20% decrease in phenylethylamine (PEA) deamination by MAO-B at a dosage of 30 mg/kg i.p. Over the range of 0.1 to 10 mg/kg i.p., CGP 6085 A decreases 5-HIAA levels in the brainstem. This in vivo inhibition of MAO activity is confirmed by in vitro experiments. In vitro studies in rat brainstem mitochondrial preparations show a dose-dependent, reversible, inhibition of MAO using tyramine as the substrate for the enzyme reaction. With an in vitro IC50 of 2-3 microM, the potency of CGP 6085 A is comparable to pargyline.     

Vascular monoamine oxidase activity in the rat brain: variation with the substrate and the vascular segment

Brain vascular monoamine oxidase (MAO) was assayed in order to determine (a) whether microvessel MAO is more or less specific for certain substrates and (b) if the extraparenchymal, pial arteries possess an MAO activity as high as that in the microvessels. Rat brain microvessels were prepared by gentle homogenisation of grey matter, followed by filtration and differential centrifugation of the matter retained. Pial arteries were carefully freed of the meninges and cut into small segments. For comparison, rat mesenteric arteries were also dissected out and cut up. MAO was assayed by measuring the rate of oxygen consumption in a small cell with a Clark electrode. Although a high microvessel MAO activity (2.2 +/- 0.3 nmol min-1 mg prot.-1) was found using noradrenaline as substrate, significantly higher rates were found with tyramine, serotonin and beta-phenyl-ethylamine. By contrast, both pial and mesenteric arteries showed a 6-7 fold lower activity (substrate tyramine). These results indicate first, that a certain specialisation of the microvessel MAO activity exists which is apparently independent of the classical A or B-form category of the substrates, and second, that the extraparenchymal vessels (pial arteries) appear to possess significantly lower MAO activity, in accordance with the concept that blood-brain properties are induced by the cerebral parenchyma.     

Effect of heat exposure on the activity of monoamine oxidase in the rat brain and interscapular brown adipose tissue

The exposure of Wistar male rats (200±20 g) to high ambient temperature (38°C) for 20 and 60 min induced an equal decrease in hypothalamic, brain stem and hippocampal monoamine oxidase activity when compared to controls. The interscapular brown adipose tissue monoamine oxidase activity, as well as oxygen consumption and rectal temperature were increased only after a 60 min heat exposure. The adrenal function, assessed by dopamine-beta-hydroxylase activity and cholesterol concentration, was enhanced both after 20 and 60 min. In conclusion, heat induced the increase in adrenal function and interscapular brown adipose tissue monoamine oxidase activity, but the decrease in that of the brain.     

Influence of culture conditions on monoamine oxidase A and B activity in rat astrocytes

Astroglial cells dispersed from newborn rat hemispheres were established in medium supplemented with 20 per cent fetal calf serum (FBS) and then grown to a confluent monolayer in the presence of 10 per cent FBS or charcoal-stripped FBS (CS). Type 1 astrocytes were subcultured and either maintained under the same conditions of the primary cultures or converted to serum-free chemically defined medium (CDM). No differences were found in either MAO A or MAO B activity of astrocytes grown in the presence of FBS or CS after 15 and 21 days in vitro (day 1 and 6 of subculture). In contrast, on day 21 both MAO A and MAO B activities were markedly higher in astrocytes subcultured in CDM compared with cells maintained in serum-supplemented medium. This difference appeared to be due to increased number of enzyme molecules, since kinetic analysis showed an increase in V_max of both MAO isoenzymes in serum-free medium, but no change in K_m. Consistently, the recovery of MAO A and MAO B activity after irreversible enzyme inhibition by clorgyline and deprenyl was faster in CDM than in FBS-supplemented medium, indicating enhanced enzyme synthesis under serum-free condition. Estimates of half-lives for the recovery of MAO A and MAO B activity indicated that, under both culture conditions, type A activity had a higher turnover rate than type B. The effect of CDM on astrocyte MAO does not appear to be due to selection of a subpopulation of cells, but rather linked to a morphological change (differentiation) with increased synthesis of both MAO isoenzymes.