Showing papers on "Monoamine oxidase B published in 1985"
TL;DR: Blockage of dopamine uptake by mazindol prevents MPTP-induced damage to nigrostriatal dopamine neurons, indicating that MPP+ concentration into dopamine neurons explains their selective destruction by MPTP.
Abstract: N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathological and clinical abnormalities in humans, monkeys, and mice that closely resemble idiopathic parkinsonism. N-Methyl-4-phenylpyridine (MPP+), a metabolite of MPTP formed by monoamine oxidase B, is accumulated into striatal and cerebral cortical synaptosomes by the dopamine and norepinephrine uptake systems, respectively, whereas MPTP itself is not accumulated. The potencies of drugs in inhibiting [3H]MPP+ or [3H]dopamine uptake into striatal synaptosomes are very similar, as are potencies in inhibiting [3H]MPP+ or [3H]norepinephrine uptake into cortical synaptosomes. The Km values for [3H]MPP+ uptake are 170 and 65 nM and the Vmax values are 2 and 0.1 nmol/g of tissue per min in rat striatum and cortex, respectively, similar to values for [3H]dopamine uptake, Autoradiography of accumulated [3H]MPP+ in slices of rat brain shows high densities in the caudate-putamen and nucleus accumbens. Furthermore, blockade of dopamine uptake by mazindol prevents MPTP-induced damage to nigrostriatal dopamine neurons, indicating that MPP+ concentration into dopamine neurons explains their selective destruction by MPTP.
1,262 citations
TL;DR: These data illustrate the physiological independence of MAO A and B and show that neurons may be specialized for their degradative as well as their synthetic functions.
Abstract: Monoclonal antibodies specific for monoamine oxidase (MAO) A and MAO B, respectively, were used to localize these enzymes in primate brain. The reagents recognized different populations of neurons: those that recognized MAO A were located in cell groups containing catecholamines, including the substantia nigra, nucleus locus coeruleus, nucleus subcoeruleus, and the periventricular region of the hypothalamus, whereas those that recognized MAO B were observed in serotonin regions, including the nucleus raphe dorsalis and nucleus centralis superior. These data illustrate the physiological independence of MAO A and B and show that neurons may be specialized for their degradative as well as their synthetic functions.
496 citations
TL;DR: Results are consistent with the premise that MPP+, formed from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by the enzyme monoamine oxidase B, may be responsible for the toxicity observed after MPTP administration.
91 citations
TL;DR: In vitro oxidation of 1‐Methyl‐4‐phenyl‐ 1,2,5,6 ‐tetrahydropyridine and the fact that MAO‐B inhibitors can protect against MPTP‐induced dopami nergic neurotoxicity in vivo point to an important role for MAO-B in MPTP metabolism in vivo.
Abstract: 1-Methyl-4-phenyl- 1,2,5,6 -tetrahydropyridine (MPTP) is a chemical that, after injection into experimental animals, including mice and monkeys, causes a degeneration of the nigrostriatal pathway. We carried out experiments designed to study the in vitro oxidation of MPTP by mouse brain mitochondrial preparations. MPTP was actively oxidized by the mitochondrial preparations, with Km and Vmax values very similar to those of benzyl amine, a typical substrate for MAO-B. MPTP was oxidized considerably better than many of its analogs, even those with relatively minor structural changes. Several monoamine oxidase inhibitors (MAOI) were potent inhibitors of MPTP oxidation, and there was a highly significant correlation between the capacity of the MAOI tested to inhibit MPTP oxidation and benzylamine oxidation. There was no correlation between the capacity of the MAOI to inhibit MPTP oxidation and their capacity to inhibit the oxidation of tryptamine, a substrate for MAO-A. In other experiments, MPTP was an excellent substrate for pure MAO-B, prepared from bovine liver. All of these data. combined with the fact that MAO-B inhibitors can protect against MPTP-induced dopami nergic neurotoxicity in vivo. point to an important role for MAO-B in MPTP metabolism in vivo.
83 citations
TL;DR: Two selective and potent inhibitors of monoamine oxidase (MAO) type B, given to mice prior to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) protected against the neurotoxic effects of MPTP.
75 citations
TL;DR: It is reported that MPTP, as well as its oxidation products, MPDP+ and MPP+, the 4-phenylpyridinium form, are also potent reversible, competitive inhibitors of both monoamine oxidase A and B, particularly the former, and that the order of inhibition for the A enzyme is MPDP+.
73 citations
TL;DR: These studies support the hypothesis that MPTP is oxidized in primate brain by MAO B to MPDP+ which is then converted to MPP+ a major metabolite found in the substantia nigra.
71 citations
64 citations
TL;DR: Lower platelet MAO activities have been reported in schizophrenia, bipolar affective disorders, alcoholism, cycloid psychoses, attention deficit disorder in children, epilepsy, insulin-dependent diabetes, Lesch-Nyhan syndrome, migraine headache, iron deficiency anemia, riboflavin deficiency, Down's syndrome, toxemia of pregnancy and thyrotoxicosis.
59 citations
TL;DR: Four new anti-MAO monoclonal antibodies are described which reveal unique epitopes on human MAO A not shared by MAO B, and at least one epitope onMAO B not sharedBypassing antimouse IgG and Staphylococcus aureus reveals immunochemical differences which support the hypothesis thatMAO A and MAOB are different proteins, presumably isozymes.
Abstract: Monoamine oxidase (EC 1.4.3.4; MAO) is the primary enzyme responsible for the intraneuronal degradation of biogenic amines in the central nervous system. An understanding of the physiological significance of the functional and regulatory differences between the two forms of the enzyme, MAOs A and B, would be facilitated by the availability of antibodies specific for the two forms of the enzyme. We previously isolated and characterized a monoclonal antibody (MAO B-1C2, previously designated MAO-1C2) which binds human MAO B but not A. We describe here four new monoclonal antibodies (designated MAO A-3C9, A-4F10, A-7B10, and A-7E10) which were elicited to highly purified MAO A from human placenta and which, in the presence of antimouse IgG and Staphylococcus aureus, immunoprecipitate greater than 90% of the catalytically active purified MAO A. MAO A-3C9 appears to have a lower affinity for purified MAO A than the other three antibodies and does not immunoprecipitate either MAO A or MAO B from human platelets or from Triton X-100 extracts of human placental and liver mitochondria. MAO A-4F10, A-7B10, and A-7E10 immunoprecipitate catalytically active MAO A from Triton X-100 extracts of human placental and liver mitochondria, but not catalytically active MAO B from either pletelets or from Triton X-100 extracts of human liver mitochondria. Collectively, these anti-MAO monoclonal antibodies reveal unique epitopes on human MAO A not shared by MAO B, and at least one epitope on MAO B not shared by MAO A. These immunochemical differences support the hypothesis that MAO A and MAO B are different proteins, presumably isozymes.
TL;DR: It is suggested that MPP+ is a simple inhibitor of MAO-A andMAO-B, but MPTP might be a 'suicide substrate' inhibitor for MAo-B.
TL;DR: D-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme and mixed-type inhibition patterns were obtained.
Abstract: Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results support the concept that MPTP accumulates in serotonergic neurons where it is oxidized by monoamine oxidase B to MPP+, which is released and then is selectively accumulated in dopaminergic neurons via the dopamine uptake system.
TL;DR: It is suggested that a small amount of striatal MAO A is present in kainic acid-sensitive postsynaptic striatal neurons and that MAO B is probably localized in both neurons and astrocytes.
TL;DR: Findings support the importance of MAO-B in the toxicity of MPTP and suggest that resistance of rat DA neurons to the neurotoxin is probably not due to species differences in MAO -B activity.
TL;DR: The restitution and long-term maintenance of full scale sexual activity in aged male rats continuously treated with (-)Deprenyl and the clinical observation that this drug prolongs in a statistically significant manner, the duration of the Parkinson's disease support the view that (-)deprenyl may improve deteriorating functions due to dopamine deficiency in the aging brain.
TL;DR: The authors present eight cases of delirious syndromes apparently attributable to the combination of monoamine oxidase inhibitors and tryptophan, a recognized antidepressant regimen.
Abstract: The combination of monoamine oxidase inhibitors and tryptophan--a recognized antidepressant regimen--has been reported to cause behavioral or neurologic toxicity. The authors present eight cases of delirious syndromes apparently attributable to this combination of agents.
Journal Article•
TL;DR: A robust, sensitive and reliable radiochemical assay for monoamine oxidase is described, and the procedures necessary to ensure the validity of the results obtained are discussed.
Abstract: A robust, sensitive and reliable radiochemical assay for monoamine oxidase is described, and the procedures necessary to ensure the validity of the results obtained are discussed. Methods for determining the activities of the two forms of monoamine oxidase, A and B, separately, are outlined and some alternative assay methods are considered.
TL;DR: It was shown that this assay of MAO in whole blood is in fact a determination of platelet MAO, and no reversible endogenous inhibitors are present in the blood.
TL;DR: The marked difference between the pharmacological effects of MDL 72145 andl-deprenyl despite equivalent inhibition of MAO B suggests that many of the Pharmacological actions ofl-Deprenyl result from its amphetaminelike sympathomimetic properties.
Abstract: The pharmacological properties of two selective inhibitors of monoamine oxidase (MAO) type B, L-deprenyl and MDL 72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine, HCl], have been investigated in rats and mice in relation to their effects on MAO. Selective inhibition of MAO B achieved following 18 h pretreatment with L-deprenyl and/or MDL 72145 did not per se lead to prominent pharmacological activity; no effects were seen in the mouse "Behavioural Despair" test, hypothermia induced by reserpine in mice was neither prevented nor reversed and there was no change in the cardiovascular responsiveness of the pithed rat to tyramine, noradrenaline or stimulation of the spinal sympathetic outflow. L-Deprenyl differed from MDL 72145 in that short term treatment with this drug caused positive effects in the "Behavioural Despair" test, reversal of reserpine hypothermia, indirect sympathomimetic stimulation of blood pressure and heart rate in the pithed rat and ipsilateral rotation in rats with unilateral nigro-striatal lesions. Qualitatively similar effects were seen with dexamphetamine. The marked difference between the pharmacological effects of MDL 72145 and L-deprenyl despite equivalent inhibition of MAO B suggests that many of the pharmacological actions of L-deprenyl result from its amphetamine-like sympathomimetic properties. MDL 72145 can, therefore, be considered a more reliable tool with which to explore the functional importance of MAO B inhibition in experimental animals and man.
TL;DR: The results suggest that L-deprenyl's antidepressant effects are mediated by some mechanism other than, or in addition to, MAO B inhibition.
TL;DR: Electrophoretic analysis of the peptides produced by limited proteolysis with bovine trypsin, alpha-chymotrypsin), Staphylococcus aureus V8 proteinase and cyanogen bromide indicate that monoamine oxidases A and B have different amino acid sequences.
TL;DR: It is reported that [3H]MPTP is rapidly converted in vitro into 1-methyl-4-phenyl-pyridinium (MPP+) by human platelet MAO-B, which is a critical feature in the neurotoxic process of MPTP.
TL;DR: The effect of 18 different amines, two mercaptans, and two alcohols on the reactivation of N-cyclopropylbenzylamine- (N-CBA-) inactivated bovine liver monoamine oxidase (MAO) is described.
Abstract: The effect of 18 different amines, two mercaptans, and two alcohols on the reactivation of N-cyclopropylbenzylamine- (N-CBA-) inactivated bovine liver monoamine oxidase (MAO) is described. All of the compounds that reactivate the enzyme produce a time-dependent pseudo-first-order return of enzyme activity and exhibit saturation kinetics. There is no direct correlation between the ability of a compound to serve as a substrate for native MAO and its ability to reactivate N-CBA-inactivated MAO. Amines containing an aromatic moiety, in general, are better reactivators than the aliphatic amines. The amine must be primary or secondary in order for reactivation to occur. The distance between the aromatic portion and the amino group is critical to the reactivation properties of the compound. The mercaptans and alcohols do not reactivate N-CBA-inactivated MAO, nor do they interfere with the reactivation reaction by benzylamine. Three mechanisms for the reactivation reaction are considered. One involves initial Schiff base formation with the active site adduct produced by N-CBA inactivation of MAO followed by base-catalyzed beta-elimination to the imine of acrolein. The second mechanism is the same as the first except no prior Schiff base formation is invoked. The third mechanism is an SN2 displacement by the amine of the active site amino acid residue attached to the adduct. Experiments are carried out to exclude the SN2 mechanism. The results of the reactivation experiments favor the Shiff base mechanism.
TL;DR: The results suggest that MAO activity and expression of MAO B activity are regulated in NG108‐15 cells in a cyclic AMP‐dependent manner.
Abstract: The total activities of monoamine oxidase (MAO) and the ratio of type B/type A activities were determined in mouse neuroblastoma N1E-115 cells, and in NX31T and NG108-15 hybrid cells derived from mouse neuroblastoma × rat sympathetic ganglion hybrid or mouse neuroblastoma × rat glioma hybrid cells. N1E-115 and NX31T cells possessed type A activities exclusively, although NG108-15 cells showed both type A (65–90%) and type B (10–35%) MAO activities. The activity of type A MAO in NX31T and N1E-115 cells was relatively constant during culturing periods in the presence or absence of dibutyryl cyclic AMP (Bt2cAMP), whereas total MAO activity and the ratio of type B MAO/type A MAO in NG108-15 cells increased as a function of culture periods. Prostaglandin E1 (PGE1) and theophylline, the best known combination to increase intracellular cyclic AMP content of NG108-15 cells, caused similar increases of MAO and of the type B/type A ratio in NG108-15 cells. The results suggest that MAO activity and expression of MAO B activity are regulated in NG108-15 cells in a cyclic AMP-dependent manner.
TL;DR: The negative correlation between age-associated changes in rat pineal melatonin and brain MAOB suggests the possibility of melatonin influence on MAO-B activity, and this report represents the attempt to explore such a possibility.
TL;DR: The observed difference in the efficiencies of the photodependent inactivation of the two types of MAO by FNPA suggests that there is a conformational or a structural difference inThe active sites of theTwo types ofMAO.
TL;DR: Both molecular forms of MAO, MAO A and MAO B, are present in single nerve cell as shown by clorgyline, a selective inhibitor ofMAO A molecular form.
TL;DR: Liver samples from patients with a prior history of alcoholism showed significantly lower monoamine oxidase activity with both phenylethylamine and serotonin as substrates, while postmortem brain samples were not different in the two groups.
Abstract: Monoamine oxidase activity in human postmortem brain and liver samples was measured in a group of patients with a prior history of alcoholism and compared to a control group with no prior history of alcoholism. Liver samples from patients with a prior history of alcoholism showed significantly lower monoamine oxidase activity with both phenylethylamine and serotonin as substrates. Postmortem brain samples, however, were not different in the two groups.