Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:001709 (MAO-A)
 2,432 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.
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PMID:Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement. 128 22

In the rat heart, monoamine oxidase (MAO)-B activity was shown to predominate in 2- to 3-week-old animals, whereas MAO-A activity was reported to be very low in newborn rats and to increase considerably with age until it predominates. These results are in contrast with those found in the mouse heart, where an age-dependent increase in MAO-B activity with no changes in 5-hydroxytryptamine deaminating activity was found to occur. There is evidence that the adult values of MAO activity are reached early in development in rat kidney and liver. In the rat lung the adult values of MAO-A activity are reached by day 40, whereas MAO-B activity is still increasing by day 80. Important differences have been reported in the developmental pattern of the two forms of MAO in the rat and mouse brain, with a decrease in the MAO-A/MAO-B ratio during postnatal development. In the human brain, the ontogenetic development of MAO-A and MAO-B appears to parallel that observed in the rodent brain. It is worth noting that most of the available data have to be considered with reservation owing to many methodological problems. Further studies are clearly needed to get reliable information on the ontogenesis of MAO in mammalian tissues.
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PMID:Developmental aspects of the monoamine-degrading enzyme monoamine oxidase. 130 8

The present work has examined the distribution of the two isoforms of monoamine oxidase (MAO), type MAO-A and MAO-B, in the cortex and medulla of the human and rat kidney. Homogenates of renal cortex and renal medulla were prepared in 67 mmoles l-1 phosphate buffer (pH = 7.2) and MAO activity was determined with [3H]5-hydroxytryptamine ([3H]5HT) and [14C]beta-phenylethylamine ([14C]beta-PEA) as preferential substrates of type A and type B MAO, respectively. Km and Vmax values for the two substrates were also calculated. Both MAO-A and MAO-B are present in the cortex and the medulla of the human and rat kidneys. In the human kidney, MAO-A activity was found to be similar in the cortex (Vmax = 142.70 +/- 45.05 nmoles mg-1 protein h-1) and medulla (Vmax = 133.91 +/- 35.51 nmoles mg-1 protein h-1); MAO-B activity was found to be higher in the cortex (Vmax = 166.19 +/- 19.75 nmoles mg-1 protein h-1) than in the medulla (Vmax = 92.91 +/- 13.22 nmoles mg-1 protein h-1). In the rat kidney, MAO-A was also found to be similar in the cortex (Vmax = 62.35 +/- 1.74 nmoles mg-1 protein h-1) and the medulla (Vmax = 59.42 +/- 0.97 nmoles mg-1 protein h-1) and higher than the activity of MAO-B in the two renal areas (cortex, Vmax = 31.06 +/- 1.09 nmoles mg-1 protein h-1; medulla, Vmax = 14.93 +/- 0.97 nmoles mg-1 protein h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Type A and B monoamine oxidase activities in the human and rat kidney. 152 23

Levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites, and the activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and monoamine oxidase A and B (MAO-A and MAO-B) have been determined in the rat posterior thalamus after enucleation during postnatal development. DA and 5-HT turnover rate have been measured as 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) accumulation rates after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015). The major changes were an increase in noradrenergic and serotoninergic metabolism in enucleated animals compared with control animals. A decrease of the MAO-A to MAO-B ratio during postnatal development was found.
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PMID:Effects of neonatal bilateral eye enucleation on postnatal development of the monoamines in posterior thalamus of the rat. 168 25

The ganglionated plexus of the guinea pig pancreas was investigated by using histochemical, immunocytochemical, and tract-tracing methods in order to determine whether pancreatic ganglia are analogous to the ganglia of the enteric nervous system (ENS). Three lines of evidence suggest that the ganglia of the pancreas appear to be interconnected with one another, as are enteric ganglia. First, microinjections of the retrograde tracer Fluoro-Gold into individual pancreatic ganglia labeled the perikarya of neurons in distant pancreatic ganglia, whereas no labeling of neurons was observed if injections were placed in the connective tissue adjacent to pancreatic ganglia. Second, when the intercalating dye DiI was microinjected into single pancreatic ganglia in fixed tissues, DiI-labeled terminals were found in additional pancreatic ganglia. Finally, microinjections of the beta subunit of cholera toxin into individual pancreatic ganglia yielded similar results. The ganglionated plexus of the pancreas also expresses a diversity of transmitter content and cell type-specific localization of monoamine oxidase (MAO) that is analogous to the ENS. In common with guinea pig enteric ganglia, pancreatic ganglia contain highly varicose 5-hydroxytryptamine (5-HT)-immunoreactive axons and intrinsic neuropeptide Y (NPY)- and substance P (SP)-immunoreactive neurons. The vast majority, but not all, of SP-immunoreactive fibers in the pancreatic parenchyma also contain calcitonin gene-related peptide (CGRP) immunoreactivity. MAO-B was the primary type of MAO found in the intrinsic elements of the pancreas where it was located in neurons and fibers in the pancreatic parenchyma. In common with serotoninergic enteric neurons, MAO-B immunoreactivity was not found at the LM level in pancreatic serotoninergic neurites. In contrast, NPY- and tyrosine hydroxylase (TH)-immunoreactive perivascular axons were found to contain abundant MAO-A, but no MAO-B immunoreactivity. It is concluded that MAO-B immunoreactivity is characteristic of a portion of the intrinsic innervation of the pancreas, whereas MAO-A immunoreactivity is a marker for the extrinsic sympathetic innervation of the pancreas. Because of its receipt of a direct neural innervation from myenteric ganglia of the bowel (Kirchgessner and Gershon, '90: J. Neurosci 10:1626-1642), similar connections, transmitter content and localization of type-specific MAO, the ganglionated plexus of the pancreas should be regarded as an extension or subset of the ENS.
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PMID:Guinea pig pancreatic ganglia: projections, transmitter content, and the type-specific localization of monoamine oxidase. 171 Jun 27

Ifenprodil, which is clinically used as a cerebral vasodilator, inhibited rat brain type A (MAO-A) and type B (MAO-B) monoamine oxidase activity. It did not, however, affect rat lung semicarbazide-sensitive amine oxidase. The degree of inhibition of either form of MAO was not changed by 30 min preincubation of the enzyme preparations at 37 degrees C with ifenprodil. Modes of inhibition of MAO-A and MAO-B by ifenprodil were competitive towards oxidation of their respective substrates, 5-hydroxytryptamine and benzylamine, with Ki values of 75 microM for inhibition of MAO-A and 110 microM for inhibition of MAO-B.
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PMID:Inhibition of rat brain monoamine oxidase activity by cerebral anti-ischemic agent, ifenprodil. 192 90

(1) Homogenates of renal cortex and renal medulla of control and 6-hydroxydopamine-denervated cat kidneys were prepared. (2) Monoamine oxidase (MAO) activity was determined with [3H]-5-hydroxytryptamine [( 3H]-5HT) and [14C]-beta-phenylethylamine [( 14C]-beta-PEA) as preferential substrates for MAO-A and MAO-B, respectively. (3) The endogenous dopamine and noradrenaline tissue contents of control and chemically-denervated kidneys were compared with the MAO activities. (4) The results show that a 70% depletion of monoamine content by chemical denervation resulted only in a 23% reduction of MAO-A activity in the renal cortex, whereas MAO-B was unaffected either in the cortical or the medullary zones; in the renal medulla MAO-A activity was not changed by denervation. Most of the MAO activity in the cat kidney is of the B type (74%) and is located in the renal cortex.
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PMID:Evidence for an extraneuronal location of monoamine oxidase in renal tissues. 236 77

Two amphetamine metabolites, p-hydroxyamphetamine (p-OHA) and p-hydroxynorephedrine (p-OHN), selectively inhibited the A form of monoamine oxidase (MAO) in rat and mouse forebrain homogenates. Of these two metabolites, p-OHA inhibited MAO-A more strongly than p-OHN. This MAO-A-selective inhibition by p-OHA or p-OHN was found to be competitive with respect to deamination of its substrate, 5-hydroxytryptamine (5-HT). The degree of MAO-A inhibition was not changed by 90 min of preincubation of the enzyme preparations with either metabolite, and the activity inhibited by p-OHA after the preincubation recovered completely to the control level after repeated washing. Uptake of 5-HT or dopamine into mouse forebrain synaptosomes was highly reduced by both p-OHA and p-OHN. Both metabolites were more potent in reducing dopamine uptake than in reducing 5-HT uptake. In reduction of 5-HT and of dopamine uptake, p-OHA was more potent than p-OHN. These results indicate that p-OHA is a more selective inhibitor of brain MAO-A activity and 5-HT uptake than its subsequent metabolite, p-OHN. These two actions of p-OHA might, together with possible 5-HT efflux into the synaptic cleft, greatly contribute to head twitch, a brain 5-HT-mediated animal behavior induced by p-OHA.
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PMID:Inhibition of brain type A monoamine oxidase and 5-hydroxytryptamine uptake by two amphetamine metabolites, p-hydroxyamphetamine and p-hydroxynorephedrine. 237 May 45

A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and the area was perfused with Ringer solution while the animals were unanesthetized after at least 3 days following surgery. Concentrations of the metabolites of 3,4-dihydroxyphenylethylamine (DA) and 5-hydroxytryptamine (5-HT) in the perfusate were determined by HPLC with electrochemical detection. Levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perfusate significantly decreased after pargyline administration (50 mg/kg i.p.), which may inhibit not only monoamine oxidase (MAO)-B but also MAO-A in these high doses. The level of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) also decreased after pargyline treatment, although change in the relative level of 5-HIAA was less than that of DOPAC or HVA. To clarify the mechanisms for the metabolism of monoamines in rat striatum, highly specific MAO-A and -B inhibitors were used in the following experiments. Treatment with l-deprenyl (10 mg/kg), a specific inhibitor for MAO-B, did not cause any statistically significant change in DOPAC, HVA, and 5-HIAA levels. No significant change was found in rat striatal homogenates at 2 h after the same treatment with l-deprenyl. In contrast, low-dose treatment (1 mg/kg) with clorgyline, a specific inhibitor for MAO-A, caused a significant decrease in levels of these three metabolites in both the perfusates and tissue homogenates. In addition to the above three metabolites, the level of 3-methoxytyramine, which is an indicator of the amount of DA released, greatly increased after treatment with a low dose (1 mg/kg) of clorgyline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats. 241 8

Monoamine oxidase (MAO) type A and type B were measured using kynuramine, 3,4-dihydroxyphenylethylamine (dopamine, DA), and 5-hydroxytryptamine (5-HT, serotonin) in 20 brain areas. The highest activities were found in the striatum (caudate nucleus, putamen, globus pallidus, and substantia nigra), hypothalamus, and c-mammilare. The ratio of DA to 5-HT deamination varied in the different regions, being in favor of DA in the striatum. With kynuramine as the substrate IC50 values of a number of inhibitors indicated that l-deprenyl was far more potent an inhibitor of human brain MAO than clorgyline or harmaline. N-Desmethylpropargylindane hydrochloride (AGN 1135) was also shown to have MAO-B inhibitory selectivity similar to that of l-deprenyl. Brains obtained at autopsy from l-deprenyl-treated Parkinsonian patients showed that, whereas MAO-B was fully inhibited by the therapeutic doses of l-deprenyl, substantial MAO-A activity was still evident. These results are matched by the significant increases of DA noted in caudate nucleus, globus pallidus, putamen, and substantia nigra and the unaltered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the same regions. These data indicate that the therapeutic actions of l-deprenyl may lie in its selective inhibition of MAO-B resulting in increased brain levels of DA formed from L-dihydroxyphenylacetic acid (L-DOPA).
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PMID:Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. 242 Sep 28


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