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Monoamine oxidase in developing rat renal cortex: effect of dexamethasone treatment.

The expression of the biogenic amine degrading enzyme monoamine oxidases-A and -B depends on several factors including regional distribution, development and hormonal environment. In the present study, we investigated the expression of monoamine oxidases in developing kidney and their regulation by dexamethasone treatment. Immunoblots and enzyme assays, performed using [14C]5-hydroxytriptamine and [14C]beta-phenylethylamine as substrates for monoamine oxidases-A and -B, respectively, showed that monoamine oxidase-A is the isoenzyme largely predominant in 9-day-old rats renal cortex. Experiments performed in 5-week-old rats showed an increase in monoamine oxidase-B activity and a decrease in monoamine oxidase-A activity and substrate affinity. The changes of monoamine oxidase-A activity and affinity were mimicked by dexamethasone treatment (0.60 mg/kg body weight injected subcutaneously three times at intervals of 24 h) of 9-day-old rats. In contrast, dexamethasone administration induced a modification of monoamine oxidase-B activity opposite to that found between 9-day- and 5-week-old rats. Dexamethasone treatment did not modify immunoreactivity and mRNA corresponding to monoamine oxidases-A and -B indicating that changes of enzyme activities were unrelated to regulation of protein synthesis and mRNA turnover. These results show that monoamine oxidases-A and -B are differently expressed in developing renal cortex and are regulated by dexamethasone treatment.

Animals↗

Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase in the rat brain.

Km and Vmax values of monoamine oxidase (MAO) A and B towards 5-hydroxytryptamine were determined for rat brain homogenates after the in vitro inhibition of one of the two forms by the selective inhibitors clorgyline and l-deprenyl. Km values of 178 and 1170 microM, and Vmax values of 0.73 and 0.09 nmol . mg protein-1 . min-1 towards 5-hydroxytryptamine were found for MAO-A and -B, respectively. The Ki for 5-hydroxytryptamine as a competitive inhibitor of beta-phenethylamine oxidation by MAO-B was found to be 1400 microM. The significance of these findings is discussed.

Animals↗

A simple fluorometric assay for type B monoamine oxidase activity in rat tissues.

A simple fluorometric assay for monoamine oxidase (MAO) [EC 1.4.3.4] activity towards beta-phenylethylamine (PEA) was devised. The procedure consists in measuring the disappearance of PEA fluorometrically. The disappearance of PEA was completely inhibited by pargyline, a potent inhibitor of MAO. MAO activity for PEA was linear with 10 mg to 100 mg of liver tissue in 3 ml of reaction mixture for up to 90 min of incubation. Using this method, the V max values and the apparent Km values of MAO for PEA in several rat tissues were determined, and compared with those for benzylamine and 5-hydroxytryptamine (5-HT).

Animals↗

Acute cardiovascular response to monoamine oxidase inhibitors: a prospective assessment.

Despite the widespread use of monoamine oxidase inhibitors (MAOIs) and the well-known adverse event of hypertensive crisis, few studies have addressed the acute cardiovascular response to an MAOI dose. We prospectively measured pulse and blood pressure changes just before and at 1, 2, 3, and 4 hours after MAOI administration in 18 patients. Significant but asymptomatic increases from baseline in mean systolic and diastolic blood pressure occurred within 2 hours after MAOI administration, with return to near baseline by 4 hours. The mechanism of this reaction is unknown.

Agoraphobia↗

Enzyme histochemistry of monoamine oxidase in the heart of aged rats.

The distribution of monoamine oxidase types A and B in the heart of young (3-month-old) and aged (26-month) Wistar rats was studied by histochemical methods. In young rats, MAO activity was higher in the left ventricle than in the right. Enzyme reactivity was present within both muscle cells and the blood vessel wall. Histochemical staining was abolished by clorgyline administration. In the heart of aged rats, we observed a very remarkable increase of clorgyline sensitive MAO activity primarily at the level of myocardial cells. The right ventricle showed the highest increase of MAO reactivity.

Aging↗

Monoamine oxidase inhibitors in bipolar endogenous depressives.

Clinical lore suggests that monoamine oxidase inhibitors (MAOIs) are not effective in endogenous depression. A review of previous placebo-controlled trials of MAOI in patients with endogenous depression neither refutes nor confirms their utility in this patient group. We present patients in the depressive phase of bipolar illness refractory to treatment with tricyclics who have responded to MAOI. These open trials require confirmation in controlled studies. Bipolar illness may be a heterogeneous disorder. Presence or absence of X-linkage, low platelet MAO, or response to MAOI may indicate different forms of the disorder.

Bipolar Disorder↗

The monoamine oxidase inhibitor-tyramine interaction.

Reports of hypertensive reactions from monoamine oxidase inhibitors (MAOI) began to proliferate in the early 1960s. Asatoor did extensive research and found that the combination of an MAOI and a food containing tyramine resulted in the hypertensive interaction ("the cheese reaction"). Because of the risk of intracerebral hemorrhage and death, clinicians were hesitant to use the MAOIs. Although progress on the metabolic effects of MAOIs has been slow, use of clinical information in addition to analysis of bioactive amine content of foods has allowed the formulation of dietary recommendations, which are thought to be useful clinically in the administration of MAOIs. This has resulted in the gradual return to use of these psychotropic compounds.

Diet↗

Platelet monoamine oxidase activity in patients with Huntington's disease.

1. Platelet monoamine oxidase (MAO) activity was investigated in 30 patients with Huntington's disease and compared with the activity in a control group. 2. Significantly elevated activity was found in the patients (P less than 0.05; t-test) when same sex contrasts were carried out to account for the well known influence of sex on MAO activity. 3. The mean MAO activity in male patients was 23.5 +/- 6.0 nmol/mg protein per h and female patients was 29.5 +/- 8.9 nmol/mg protein per h using tyramine as the substrate. 4. The possible influence of environmental factors on the results is discussed.

Adolescent↗

Platelet monoamine oxidase activity in mentally disordered violent offenders.

The activity of monoamine oxidase (MAO) in blood platelets among criminals undergoing forensic psychiatric examinations was studied. As compulsiveness, disturbed perceptions of reality, etc. are states not known to be related to MAO and yet possibly cause aggressiveness and violence among psychotic patients, we divided the patients into 2 groups, psychotic and nonpsychotic offenders. There was lower MAO activity among violent offenders than among nonviolent offenders. The difference between the violent and nonviolent offenders became greater when the subjects with a history of psychosis were removed. Furthermore, in the group of psychotic offenders, there was no statistical difference between violent and nonviolent individuals in this regard.

Adult↗

A kinetic evaluation of monoamine oxidase activity in rat liver mitochondrial outer membranes.

1. A preparation of mitochondrial outer membranes from rat liver can be shown to contain two kinetically distinct monoamine oxidase activities. These activities are distinguishable by their different sensitivities to the irreversible inhibitor clorgyline, and by the effect of the reversible inhibitors benzyl cyanide and 4-cyanophenol. 2. The substrate specificities of the preparation and the two enzyme species have been elucidated.

Acetonitriles↗

Clinical symptoms and platelet monoamine oxidase in subgroups and different states of affective disorders.

Platelet monoamine oxidase activity (MAO) and clinical symptoms were examined in 116 individuals, 32 acute depressed patients and 84 healthy controls. The enzyme activity was lower in depressed women than controls. MAO activity correlated positively with rated clinical state in depressed women but not in depressed men. Patients were reexamined after 10 years and categorized into affective psychosis (endogenous) or neurotic depression (International Statistical Classification of Diseases, Injuries and Causes of Death, 1987; ICD-9). Neurotic depressed occurred frequently in the low activity group. Endogenously depressed showed positive correlation between MAO activity and rated clinical state. The association between platelet MAO activity and clinical state is discussed.

Adult↗

Time-dependent inhibition of monoamine oxidase by beta-phenethylamine.

Several reports have suggested that monoamine oxidase activity towards beta-phenethylamine is inhibited by high concentrations of that substrate. This inhibition is not found if initial velocities are measured, but there is a slower time-dependent inhibition at higher beta-phenethylamine concentrations. Such time-dependent inhibition is not found with tyramine as substrate or upon incubation of the enzyme with the reversible inhibitor amphetamine. The inhibition is not due to the accumulation of phenacetaldehyde, phenylethanol or phenacetic acid, or to a reaction of any of these three products either with each other or with beta-phenethylamine. Although the inhibition is time-dependent, the inactivated enzyme slowly regains activity upon removal of the beta-phenethylamine. A model is proposed to explain the observed inhibition.

Animals↗

Effect of maternal methadone administration on the development of multiple forms of monoamine oxidase in rat brain and liver.

The development of total monoamine oxidase (MAO) and MAO-A and MAO-B in the forebrain, brainstem, cerebellum and liver of methadone-treated and normal rats were monitored with tryptamine, serotonin and benzylamine, respectively. Daily administration of methadone (10 mg/kg, s.c.) to pregnant and nursing rats substantially retarded the development of total and the A-form of MAO in the brain regions of pups but had no effect on that of MAO-B. The effect of methadone on the development of total MAO and MAO-A in the liver was only transient and less significant. This finding indicates that the perinatal opiate syndrome associated with maternal exposure to methadone is caused by the inhibition in MAO-A development in monoaminergic neurons in the brain.

Animals↗

Activation of monoamine oxidase type-B by aluminum in rat brain homogenate.

Monoamine oxidase type B (MAO-B) activity is elevated in certain neurological diseases such as Alzheimer's and Parkinson's disease with respect to age-matched controls; the cause of this elevation is unknown. The documented accumulation of aluminum in certain neurodegenerative diseases prompted us to test the effect of Al3+ on the activity of MAO-B in rat brain homogenate. Results showed that the metal ion significantly increased MAO-B enzymatic activity in a dose-dependent manner, yielding a K(M) of 5.69 microM compared with 34.45 microM in the absence of the metal ion. The Vmax of 45.34 micromol/min was unchanged in the presence of the metal ion.

Aluminum↗

The effects of stereoisomers of 2-amino-6(7)- and 9-amino-6-trifluoromethylbenzonorbornenes on food intake, brain serotonin concentration, and monoamine oxidase activity.

To evaluate the importance of the conformation of fenfluramine in eliciting its various central nervous system effects, the isomers of 2-amino-6(7)- and 9-amino-6-trifluoromethylbenzonorbornene were employed as conformationally defined analogs of norfenfluramine. In this series of isomeric amines, the exo-2 and anti-9 isomers resemble the fully extended conformation of fenfluramine, whereas the endo-2 and syn-9 isomers resemble the folded conformation. The exo-2 and anti-9 isomers were equi-effective in reducing food intake in the rat, but were approximately seven times less potent than fenfluramine. The endo-2 and syn-9 isomers had no effect on food intake up to a dose of 40 mg/kg. All of the isomers were as effective as amphetamine in inhibiting brain monamine oxidase type B. These isomers also inhibited monoamine oxidase type A to the same extent as type B, but were significantly less potent than amphetamine in inhibiting this form of the enzyme. The effects at anorectic doses on brain serotonin (5-HT) concentration were also studied. Although fenfluramine decreased brain 5-HT concentration, the exo-2, syn-9 and anti-9 isomers had no significant effect. The endo-2 isomers caused an 11% decrease in 5-HT concentration, but this effect was observed at higher doses of the compound. The data suggest that the fully extended conformation of fenfluramine is preferred over the folded conformation for eliciting its anorectic activity. However, no conclusion can be made for the conformational requirements for the other biological responses investigated in this study.

Amphetamine↗

Classification of patients with affective disorders using platelet monoamine oxidase activity, serum melatonin and post-dexamethasone cortisol.

Platelet monoamine oxidase activity (MAO), melatonin and cortisol post-dexamethasone suppression test (DST) were examined in 28 patients with major affective disorder and in 20 controls. MAO activity was lower and cortisol post-dexamethasone was higher in depressed patients. Platelet MAO activity and cortisol in depressed and controls yielded high sensitivity (90%) and specificity (89%). The patients were re-examined after 10 years and categorized into affective psychosis or neurotic depression (ICD-9). Multidimensional analysis identified one subgroup coinciding in 92% with affective psychosis and another subgroup coinciding in 87% with neurotic depression. Combination of MAO, melatonin and post-DST cortisol may be useful in the diagnosis of subgroups of depressed patients and in choice of therapy.

Adult↗

Monoamine oxidase types A and B in the vertebrate brain.

1. Monoamine oxidase (MAO) activity was measured in brains of teleosts, amphibians a reptile, birds and mammals. Selective inhibitors were used to determine the relative proportion of MAO type A and MAO type B. 2. Brain homogenates of all tetrapods showed double sigmoid inhibition curves, indicating the presence of both forms of MAO. 3. Brain homogenates of all teleosts showed single sigmoid inhibition curves, with greater sensitivity to type A inhibitors. 4. These results indicate that tetrapod brains contain both type A and type B MAO activity, whereas teleost brains contain only a type A-like enzyme. 5. It is possible that the presence of two forms of MAO in brain may confer an advantage to a terrestrial lifestyle.

Animals↗

Direct continuous fluorometric assay for monoamine oxidase B.

The first direct and continuous fluorometric assay for monoamine oxidase B (MAO B) has been developed. E-2,5-Dimethoxycinnamylamine hydrochloride was designed and synthesized and was found to be an excellent substrate for MAO B (Km = 218 microM, Kcat = 435 min-1). This compound has an intense purple fluorescence when irradiated at lambda ex = 343 nm (lambda em = 393 nm) in Tris buffer, pH 9.0, or sodium phosphate buffer, pH 7.2, but under the same conditions, the corresponding aldehyde, the product of the MAO-catalyzed oxidation of E-,5-dimethoxycinnamylamine hydrochloride, does not fluoresce. The activity of MAO B, therefore, can be determined efficiently and rapidly by continuously following the decrease in fluorescence at 393 nm at enzyme concentrations as low as 100 nM. The change in fluorescence is linear up to a substrate concentration of 500 microM.

Animals↗