Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vitro kinetic study on inhibition of the monoamine oxidase-A (MAO-A) of the rat brain by two pyrethroids, namely permethrin (PM) and cypermethrin (CPM), has shown that PM and CPM competitively inhibit MAO-A by altering both the Michaelis-Menten constant (Km) and the maximum velocity (Vmax). Inhibitor constant values (Ki) indicated that CPM was a more effective inhibitor of MAO-A than PM. Both PM and CPM caused maximum inhibition of MAO-A at neutral pH. CPM significantly elevated the activation energy values of MAO-A as compared to those of PM.
Mol Cell Biochem 1993 Jul 21
PMID:Inhibition of monoamine oxidase-A of rat brain by pyrethroids--an in vitro kinetic study. 823 82

1. The effects of chronic administration (28 days s.c. via Alzet osmotic minipumps) of 2-phenylethylamine.HCl (10 mg kg-1 per day) and/or (-)-deprenyl.HCl (1 mg kg-1 per day) on dopamine and noradrenaline receptor subtypes have been measured in rat brain. 3H-CGP 12177 was used to label beta-adrenoceptors; 3H-spiperone and 3H-SCH 23390 were used to label D2-like and D1-like receptors. 2. Total cortical beta-adrenoceptor density was reduced by (-)-deprenyl but not 2-phenylethylamine alone. Combined administration of 2-phenylethylamine and (-)-deprenyl resulted in a significantly larger decrease than (-)-deprenyl alone. Subtype density analysis by competition experiments with ICI 89406 revealed that the (-)-deprenyl effect in cortex was due to a decrease in beta 1-adrenoceptor density. The combination of 2-phenylethylamine and (-)-deprenyl resulted in a significant decrease in both cortical beta 1- and cortical beta 2-adrenoceptors. Cerebellar beta-adrenoceptor density was not altered by the present drug treatments. The Kd values for total beta-adrenoceptor densities and Ki values for beta-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum. 3. Administration of 2-phenylethylamine and of (-)-deprenyl resulted in a decrease in the density of D1-like 3H-SCH 23390 but not D2-like 3H-spiperone binding to dopamine receptors in the striatum. The effects of combined 2-phenylethylamine and (-)-deprenyl treatment on 3H-SCH 23390 binding were additive. These drug treatments did not alter Kd values for these binding sites. 4. The down-regulation of catecholamine receptors following chronically increased availability of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attributable to a direct neuromodulatory action of 2-phenylethylamine on catecholamine receptors. 5. The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO inhibitor antidepressants on catecholamine receptor systems indicate that this substrate for MAO may mediate some of the effects of MAO inhibitor antidepressants.
Cell Mol Neurobiol 1993 Jun
PMID:Down-regulation of beta-adrenergic and dopaminergic receptors induced by 2-phenylethylamine. 824 85

Nine cysteines are found in the deduced amino acid sequences of both human liver monoamine oxidase (MAO)-A and MAO-B. The role of these cysteine residues in MAO-A and -B catalytic activity was studied by site-directed mutagenesis, whereby each cysteine residue was converted to serine. The wild-type and mutant cDNAs were then transiently transfected into COS cells and assayed for MAO-A and -B catalytic activity using 5-[3H]hydroxytryptamine and [14C]phenylethylamine, respectively, as substrates. Catalytic activities were retained in seven MAO-A cysteine to serine mutants (mutations at residues 165, 210, 266, 306, 321, 323, and 398) and in six MAO-B cysteine to serine mutants (mutations at residues 5, 172, 192, 297, 312, and 389). Kinetic parameters (Km) of these mutants were also similar to those of the wild-type enzymes, indicating that these cysteines are not necessary for enzymatic activity. Substitution of MAO-A Cys-374 and -406 and MAO-B Cys-156, -365, and -397 with serine resulted in complete loss of MAO-A and -B catalytic activity. The loss of catalytic activity was not due to unsuccessful transfection of the mutants, as indicated by either Northern blot or Western blot analysis. The loss of catalytic activity in the MAO-A Ser-406 and MAO-B Ser-397 mutants may be due to the prevention of covalent binding of the enzyme to the cofactor FAD, which is necessary for catalytic activity. The loss of catalytic activity of MAO-A Ser-374 and MAO-B Ser-156 and -365 suggests that these cysteines are important for catalytic activity, but whether they are involved in forming the active site or are important for the appropriate conformation of MAO-A and -B remains to be studied.
Mol Pharmacol 1993 Jun
PMID:Site-directed mutagenesis of monoamine oxidase A and B: role of cysteines. 831 21

Regional expression and antidepressant drug-induced regulation of mRNA encoding the serotonin (5-HT) transporter were studied in rat brain. While 5-HT transporter mRNA is abundantly expressed in the midbrain raphe complex, lower concentrations were also found in frontal cortex, hippocampus, and neostriatum using a combination of reverse transcriptase-polymerase chain reaction (RT-PCR), Southern hybridization, and sequence analysis. Long-term administration of antidepressants which inhibit 5-HT reuptake, but not monoamine oxidase inhibitors or 5-HT receptor agonists, decrease 5-HT transporter mRNA steady-state concentrations. Based on these observations, we conclude that (1) mRNA coding for the 5-HT transporter is present in several brain areas associated with ascending HT pathways, and (2) chronic treatment with reuptake inhibiting antidepressants may be associated with regulation of the 5-HT transporter at the level of gene expression which may contribute to the neuroadaptive mechanisms that likely underlie their therapeutic efficacy.
Brain Res Mol Brain Res 1993 Jan
PMID:Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants. 838 6

1. The effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding site density were measured in brain cortical membranes from male Sprague-Dawley rats. 2. The density but not the affinity of [3H]tryptamine binding sites was increased in 18-month-old rats relative to 3-month-old rats. Neither the density nor the affinity of [3H]dihydroalprenolol binding sites was affected by age. 3. Chronic administration (28 days s.c. via Alzet osmotic minipumps) of tricyclic antidepressant drugs (daily doses: imipramine.HCl, 30 mg kg-1; desipramine.HCl, 10 mg kg-1; clomipramine.HCl, 10 mg kg-1) resulted in decreases in [3H]dihydroalprenolol binding site density but no changes in [3H]tryptamine binding site density; no changes in affinity of either site were observed. 4. Chronic administration (s.c. via Alzet osmotic minipumps) of monoamine oxidase inhibitor antidepressant drugs (daily doses: tranylcypromine.HCl, 0.5 and 1.0 mg kg-1; phenelzine sulfate, 5 and 10 mg kg-1, each for 28 days; clorgyline.HCl, 1.0 mg kg-1; (-)-deprenyl.HCl, 1.0 mg kg-1, each for 14 days) resulted in decreases in [3H]tryptamine binding site density, without any effects on the affinity of this site. In addition, each of these monoamine oxidase inhibitors except (-)-deprenyl resulted in a decrease in [3H]dihydroalprenolol binding site density. No affinity changes were observed. 5. These data indicate that the [3H]tryptamine binding site exhibits physiological changes with aging and is differentially sensitive to the actions of tricyclic antidepressants and monoamine oxidase inhibitor antidepressants, respectively.
Cell Mol Neurobiol 1993 Feb
PMID:Effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding to rat cortical membranes. 838 28

The copper-containing amine oxidase from pea seedlings has been crystallized using lithium sulfate as precipitant at pH 5.2. The unit cell is orthorhombic, space group P2(1)2(1)2(1), with dimensions a = 89.3 A, b = 113.4 A, c = 199.0 A. The mass of the asymmetric unit is 131(+/- 13) kDa, consistent with independent evidence that the molecule has two approximately 66 kDa subunits. The crystals diffract to 2.5 A in a synchrotron X-ray beam.
J Mol Biol 1993 Jan 05
PMID:Crystallization and preliminary crystallographic characterization of the copper-containing amine oxidase from pea seedlings. 842 5

Structural properties of dimeric (2 x 75 kDa) copper-containing amine oxidase (EC 1.4.3.6) from Aspergillus niger were studied. The enzyme treated with SDS was dissociated into subunits which showed different mobility on polyacrylamide gel without SDS. The separated subunits had no activity but a quinone moiety was detected in both by a redox-cyclic quinone staining. After titration of the enzyme with p-nitrophenylhydrazine, which showed half-site reactivity (1 mole per dimer), and SDS treatment both p-nitro-phenylhydrazone and a remaining quinone moiety were detected in each subunit. It is suggested that the half-site reactivity with phenylhydrazine is caused by conformational changes after binding of the inhibitor to any one of the active sites leading to inaccessibility of the second active site for the inhibitor. The difference in electrophoretic mobility of the separated subunits originates probably from their structural difference likely to occur outside the active site, even if the amino acid sequences of the subunits appear to be identical.
Biochem Mol Biol Int 1995 Aug
PMID:Half-site reactivity with p-nitrophenylhydrazine and subunit separation of the dimeric copper-containing amine oxidase from Aspergillus niger. 853 92

The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.
Hum Mol Genet 1995
PMID:Norrie disease and MAO genes: nearest neighbors. 854 72

The purpose of this study was to assess biogenic amine catabolism in Amblyomma hebraeum Koch (an African cattle tick). We assayed haemolymph and saliva for a variety of biogenic amines (usually following injection of substrate into the haemolymph) in partially fed females using HPLC coupled to electrochemical detection. Dopamine (DA) and 5-hydroxytryptamine (5-HT) were rapidly converted to dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) respectively, indicating that monoamine oxidase (MAO) constitutes a major catabolic pathway for biogenic amines in this species. We could not detect N-acetylated or gamma-glutamyl conjugated metabolites of these important neurotransmitters. [In a few samples we looked for but could not detect homovanillic acid or 3-methoxytyramine (O-methylated metabolites of DOPAC and DA respectively).] Deprenyl was about 44-72 times more potent an inhibitor of MAO than clorgyline when either DA or 5-HT was offered as substrate, suggesting that this MAO is of the MAOB type. Conversion of DA to DOPAC was also detected in several tissues incubated with DA in vitro; in descending order of MAO activity (pmol mg-1 h-1 at about 18 degrees C) tissues tested were: skeletal muscle (approximately 100), Malpighian tubule (approximately 50), ovary (approximately 45), salivary gland (approximately 30), midgut (approximately 20), and haemolymph (approximately 4-5). This study suggests that ticks differ considerably from insects in utilizing MAO as an important metabolic pathway for biogenic amines.
Insect Biochem Mol Biol 1996 Jan
PMID:Catabolism of dopamine and 5-hydroxytryptamine by monoamine oxidase in the ixodid tick, Amblyomma hebraeum. 867 75

The distribution of mRNAs encoding the isoenzymes monoamine oxidase A and B (MAO-A and MAO-B) in monkey locus coeruleus and dorsal raphe nucleus was studied by in situ hybridization histochemistry using 35S-labelled oligodeoxynucleotide probes complementary to cloned human sequences. MAO-A mRNA was highly expressed in noradrenergic neurons of the locus coeruleus while MAO-B mRNA was abundantly and exclusively localized in serotoninergic neurons of the raphe. However, upon emulsion radioautography raphe neurons showed a level of MAO-A mRNA signal noticeably above the background. Our results indicate the utility of human MAO oligodeoxynucleotide probes to identify homologous species of transcripts in the brain of a non-human primate. They also suggest the coexistence of the isoenzymes in raphe neurons as well as the potential role of MAO-A in metabolizing serotonin in vivo.
Brain Res Mol Brain Res 1996 Mar
PMID:Detection of MAO-A and MAO-B mRNAs in monkey brainstem by cross-hybridization with human oligonucleotide probes. 896 58


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