Showing papers on "Monoamine oxidase B published in 1974"

The monoamine oxidases of brain: selective inhibition with drugs and the consequences for the metabolism of the biogenic amines

Abstract: Two types of monoamine oxidase were identified in vivo in rat brain. These enzymes, designated as type A and type B, were inhibited differentially by the drugs clorgyline (inhibitor of type A enzyme) and deprenyl (inhibitor of type B enzyme). With these drugs, we have shown that the two types of enzyme are responsible for the metabolism of different amines in vivo and that the metabolism of the amines can be altered selectively by administration of these drugs. For example, norepinephrine and serotonin were perferred substrates for type A enzyme and injection of clorgyline induced an elevation of these amines in brain. β-Phenylethylamine was a preferred substrate for type B enzyme and injection of deprenyl slowed the metabolism of β-phenylethylamine in brain. In contrast to the aforementioned amines, dopamine was a substrate for both enzymes and injection of either drug resulted in elevated dopamine concentrations. From our studies, we postulate that it may be possible to alter selectively the metabolism of the putative transmitter amines in man by administration of monoamine oxidase inhibitor drugs that preferentially inactivate a specific type of monoamine oxidase.

Studies of monoamine oxidases: properties of the enzyme in bovine and rabbit brain mitochondria.

Abstract: Brain mitochondria were prepared from rabbit and bovine cerebral cortex and the purity and intactness of the preparation assessed through the use of enzyme markers and electron microscopy. Enzymatic properties of monoamine oxidase were studied in the purified mitochondrial preparations which were essentially devoid of major contamination by other organelles, especially microsomes. Five substrates were used for characterization of the enzyme: dopamine, kynuramine, serotonin, tryptamine and tyramine. It was found that there was considerable substrate variation in the properties, but in general, the two species showed similar characteristics. The more pertinent findings were: (1) apparent Km values ranged from 1.1 ± 10−5m for tryptamine to 2.5 ± 10−4m for dopamine; (2) substrate specificity from Vmax values in decreasing order was tyramine > dopamine > kynuramine > serotonin > tryptamine for the bovine enzyme and tyramine > kynuramine > dopamine > serotonin > tryptamine for rabbit; (3) there appeared to be three distinct pH optima according to substrate: pH 7.5 for phenylethylamines, pH 8.2–8.5 for the indolylamines and pH 9.1 for kynuramine; and (4) the activity with tyramine was highly sensitive to increased oxygen tension while kynuramine showed no sensitivity. It is proposed that the properties of monoamine oxidase, a membrane-bound enzyme, might be influenced by the microenvironment and results are also discussed in terms of multiple forms or multiple activity sites on a single form.

2-Phenylethylamine as a possible mediator for Δ 9 -tetrahydrocannabinol-induced stimulation

Abstract: IF neuroamines modulate perception and affect, as implied in much of the literature, the behavioural effects of marihuana may be mediated by alterations of brain amine mechanisms, Even in large doses (5–500 mg kg−1), Δ9-tetra-hydrocannabinol (Δ9-THC) produces only relatively small changes in the brain levels and turnover of serotonin1–3, catecholamines2–4 and acetylcholine5. We report here biochemical and behavioural experiments suggesting a role for endogenous 2-phenylethylamine (PEA) in the action of Δ9-THC. PEA may be one of the neuromodulators involved in wakefulness, arousal and excitement6,7, and it is the precursor of phenylethanolamine, a putative neurotransmitter8. PEA is present in human8 and animal9 brain; monoamine oxidase B plays a major role in the metabolism of PEA whereas monoamine oxidase A is responsible for the deamination of noradrenaline and serotonin10. The observations that the urinary excretion of PEA is decreased in patients with endogenous depression11–13 and that in animals brain levels of PEA are increased by antidepressive treatments [monoamine oxidase inhibitors (MAOIs), imipramine, electroshock7,9,14] suggest that this amine is important in modulating affect.

Monoamine oxidase and cerebral uptake of dopaminergic drugs.

Abstract: The brain uptake of amines that do not enter the brain or enter it poorly was promoted by noncompetitive inhibitors of monoamine oxidase, as shown by behavioral and chemical criteria. Mice pretreated with water or enzyme inhibitors other than those mentioned were placid after receiving dopamine (3,4-dihydroxyphenethylamine). Mice pretreated with monoamine oxidase inhibitors (nialamide or iproniazid) showed upon treatment with dopamine the brisk motor responses characteristic of treatment with its precursor, L-dopa (3,4-dihydroxyphenylalanine). After receiving dopamine, intact nialamide-pretreated mice showed marked increases of brain dopamine, in contrast to water-pretreated test mice or water-treated controls. In unilaterally caudectomized, nialamide-pretreated mice, dopamine induced marked lateral curving of the body toward the lesion followed by running in that direction. Noradrenaline or adrenaline induced curving in caudectomized mice, whereas intact ones remained placid. These catecholamines are bound and inactivated by monoamine oxidase. The cerebral uptakes of chemicals that are bound but not inactivated by monoamine oxidase were thereafter tested. Nialamide induced increased behavioral responses to apomorphine and to N-propyl noraporphine, increased cerebral concentrations of both, and a deep coloration of the brain from methylene blue (bound by monoamine oxidase) but not Evans blue (bound by albumin). Even large doses of nialamide, however, failed to affect the behavioral responses to oxotremorine, which has cholinergic rather than adrenergic or dopaminergic properties. Mitochondrial monoamine oxidase seems therefore to play a specific regulatory role in the transport of substances that it binds, either to inactivate or to release them.

Catechol-o-methyltransferase and plasma monoamine oxidase in patients with affective disorders.

Abstract: This communication is an extension of a preliminary report (Mattsson et al. (1972)) of a study of catechol-o-methyltransferase (COMT) activity in red blood cells and monoamine oxidase (MAO) activity in plasma in patients suffering from affective disorders and in controls. Both COMT and MA0 are important enzymes in the metabolism of biogenic amines, and their activities in blood may be of interest as possible indices of the corresponding enzyme activities elsewhere in the body, e.g. in the brain. In the blood COMT can be found in the erythocytes in significant amounts (Axelrod G.’ Cohn (1971)). M A 0 is present in the platelets, probably bound to the mitochondria (Salatunturi G.’ Paasonen (1966)), and in plasma in a soluble form. The platelet-bound MA0 seems to be similar in some respects t o the nclassicaln mitochondria1 M A 0 (Robinson et al. (1968), (Collins & Sandler (1971)), while the plasma MAO, although its substrate specificity partially overlaps that of the classical enzyme, is a different protein, the physiological function of which has not yet been established (McEwen (1972)).

Monoamine Oxidase Activity: A Genetic Marker of Schizophrenia?

Abstract: The results of pilot studies of the activities of platelet monoamine oxidase {MAO) and catechol0-methyl transferase (COMT) in the blood of selected schizophrenics and the families of schizophrenics is presented. No statistically significant difference was found between the blood COMT levels of 21 control subjects and 26 schizophrenics, whereas the values found for platelet MAO activity were significantly lower for the schizophrenic group than for the control group. In one acutely disturbed first-admission schizophrenic the platelet MAO activity increased to a normal level in parallel with the clinical improvement, whereas in the relapsing schizophrenics the platelet MAO activity remained at its initial level although the clinical picture improved. No consistent findings with regard to the platelet MAO activity emerged from the study of 3 families having a history of schizophrenia.