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Biomedical subjects

M Naoi

Publications and source records attributed to M Naoi.

At least 163 records · Page 9Linked to original sources
PubMed1988

4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase.

4-(O-Benzylphenoxy)-N-methylbutylamine (Bifemelane, BP-N-methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes. It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively. BP-N-methylbutylamine had a much higher affinity to MAO-A than an amine substrate, kynuramine, and it was a more potent inhibitor of MAO-A than of MAO-B. The Ki values of MAO-A and -B were determined to be 4.20 and 46.0 microM, respectively, while the Km values of MAO-A and -B with kynuramine were 44.1 and 90.0 microM, respectively. The inhibition of MAO-A and -B by BP-N-methylbutylamine was found to be reversible by dialysis of the incubation mixture. MAO-A in human placental and liver mitochondria and in a rat clonal pheochromocytoma cell line, PC12h, was inhibited competitively by BP-N-methylbutylamine, while MAO-B in human liver mitochondria was inhibited noncompetitively, as in human brain synaptosomes. BP-N-methylbutylamine was not oxidized by MAO-A and -B. The effects of other BP-N-methylalkylamines, such as BP-N-methylethylamine, -propylamine, and -pentanylamine, on MAO activity were examined. BP-N-methylbutylamine was the most potent inhibitor of MAO-A, and BP-N-methylethylamine and -propylamine inhibited MAO-B competitively, whereas BP-N-methylbutylamine and -pentanylamine inhibited it noncompetitively. Inhibition of these BP-N-methylalkylamines on MAO-A and -B is discussed in relation to their chemical structure.

Adrenal Gland Neoplasms↗
PubMed1988

[A case of remarkable regression of a colonic cancer involving metastasis to the liver as a result of FT-207 treatment].

In mid-August, 1986, a 50-year-old man underwent a detailed examination following the finding of a tumor in the upper abdominal region. The tumor was revealed to be a sigmoid colon cancer with multiple metastasis to both halves of the liver. Subsequent administration of FT-207 suppositories (750 mg X 2/day) resulted in a recognizable shrinkage of the metastatic lesions in the liver after one month, and a barium enema a month later indicated a decrease in the size of the original tumor. The pre-operative CEA value was 2,317 ng/ml, but this has reduced to 46.7 ng/ml to date March, 1987. In this report of single chemotherapy treatment with FT-207 of a sigmoid colon cancer involving metastasis to the liver, the prognosis obtained for the original and hepatic lesions has been good, and the patient's course to date healthy.

Adenocarcinoma↗
PubMed1987

Metabolism of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in a rat pheochromocytoma cell line, PC12h.

The uptake and metabolism of a neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were examined in a rat pheochromocytoma cell line, PC12h. These cells which contain only type A monoamine oxidase (MAO-A) oxidize MPTP into N-methyl-4-phenylpyridinium ion (MPP+). By kinetic analysis, the apparent Km value and the maximal velocity of the MPP+ production are 70.4 +/- 6.5 microM and 38.3 +/- 10.0 pmol/min/mg protein, respectively. After 7 days of culture in the presence of MPTP, the cells could oxidize from 25 to 50% of the MPTP added to the culture medium and could accumulate MPP+. The intracellular concentrations of MPTP were almost the same after 7 days of culture in the presence of MPTP from 10 nM to 100 microM. The cells could survive 7 days after exposure to up to 100 microM MPTP. Tyrosine hydroxylase (TH) and MAO activity were not affected by the presence of MPTP. Dopamine (DA) concentrations and a nonspecific enzyme, beta-galactosidase activity in the cells were not affected by the addition of MPTP. These data show that the uptake and oxidative conversion of MPTP take place in the cells having MAO-A alone, and that the neurotoxicity of MPP+ may not be due directly to its storage in subcellular compartments.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Binding of specific glycoconjugates to human brain synaptosomes: studies using glycosylated beta-galactosidase.

Using glycosylated beta-galactosidase (beta-gal) as a glycoprotein model, binding of glycoconjugates to human brain synaptosomes was studied. Out of beta-gal modified with a series of p-aminophenyl alpha- or beta-glycosides, beta-gal modified with p-aminophenyl beta-D-glucopyranoside (beta-D-Glc beta-gal) was bound to the synaptosomes most effectively, then beta-gal modified with beta-D-galactoside and with alpha-D-mannoside. Kinetic studies on the binding of beta-D-Glc beta-gal indicated the presence of saturable binding on human brain synaptosomes. The values of the apparent Km and of the maximal binding velocity were obtained to be 248 +/- 32.9 microM and 43.8 +/- 1.43 fmol/min/mg synaptosome protein, at 4 degrees C and pH 7.5. The specificity of the sugar recognition site proved by the competitive inhibition of the binding of beta-D-Glc beta-gal by bovine serum albumin modified with the same glycoside. The binding of beta-gal modified with beta-D-galactoside was inhibited by treatment of the synaptosomes with trypsin, phospholipase A2, C and D, and with neuraminidase, while the binding of beta-D-Glc beta-gal was inhibited by neuraminidase treatment of synaptosomes. In subcellular fractions of human brain the binding protein was localized mainly in synaptosomes.

Cerebral Cortex↗
PubMed1987

1,4-Benzoquinone as a new inhibitor of monoamine oxidase.

The effect of 1,4-benzoquinone (BQ) on type A and B monoamine oxidase (MAO-A and -B) in human brain synaptosomes was examined. MAO-A was found to be markedly inhibited by BQ competitively with the substrate, kynuramine, while MAO-B was less sensitive to this inhibitor and the inhibition was non-competitive with the substrate. The Ki value of MAO-A (9.62 +/- 0.35 microM) was much smaller than the Km value of the enzyme with the substrate (56.3 +/- 3.5 microM) or the Ki value of MAO-B with BQ (20.3 +/- 0.9 microM). The inhibition of MAO-A by BQ was also confirmed by the use of platelet mitochondria and clonal rat pheochromocytoma PC12h cells as enzyme sources. The inhibition of MAO activity by BQ proved to be reversible: the inhibited enzyme activity could be recovered by column chromatography on Sephadex G-25.

Adrenal Gland Neoplasms↗
PubMed1987

A fluorometric determination of N-methyl-4-phenylpyridinium ion, using high-performance liquid chromatography.

A simple and sensitive assay procedure for the quantitation of N-methyl-4-phenylpyridinium ion (MPP+), a neurotoxin, was devised using its fluorescence and high-performance liquid chromatography (HPLC). The fluorescence intensity of MPP+ was several thousand times more than that of N-methyl-1,2,3,6-tetrahydropyridine (MPTP), a metabolic precursor of MPP+. This method was found to be sensitive enough to measure less than 10 pmol MPP+ without using HPLC and 10 fmol using HPLC. The oxidation of MPTP by monoamine oxidase in human brain synaptosomal mitochondria was examined by this assay method. This fluorometric-HPLC method should have broad application in the study of the neurotoxin MPP+.

1-Methyl-4-phenylpyridinium↗
PubMed1987

Quinoline and quninaldine as naturally occurring inhibitors specific for type A monoamine oxidase.

Type A monoamine oxidase (MAO-A) in human placental mitochondria was competitively inhibited by naturally occurring substances, quinoline and quinaldine, using kynuramine as substrate. Quinoline had a higher affinity for MAO than kynuramine. MAO-A in human brain synaptosomal mitochondria was also competitively inhibited by quinoline, while type B MAO (MAO-B) was reversibly and non-competitively inhibited by quinoline. Quinoline inhibited MAO-A much more potently than MAO-B. Of several compounds structurally similar to quinoline, isoquinoline noncompetitively inhibited MAO-A and -B activity.

Binding, Competitive↗
PubMed1987

L-threo-3,4-dihydroxyphenylserine (DOPS) aldolase: a new enzyme cleaving DOPS into protocatechualdehyde and glycine.

An enzyme which cleaves L-threo-3,4-dihydroxyphenylserine into protocatechualdehyde and glycine was demonstrated in extracts of human brains. Equimolar production of protocachualdehyde and glycine was quantitatively confirmed using high-performance liquid chromatography. In subcellular fractions of the brain, the highest enzyme activity was found in cytosol and soluble fraction. L-threo-DOPS proved to be the best substrate for this enzyme. The L-erythroisomer was less active and D-threo- and D-erythro-isomers were essentially inactive. The enzyme activity has an optimal pH around 7.4, and requires pyridoxal phosphate for maximal activity.

Aldehyde Dehydrogenase↗
PubMed1987

Quinolinic acid: an endogenous inhibitor specific for type B monoamine oxidase in human brain synaptosomes.

Quinolinic acid (QUIN), a well-known excitotoxin, was found to inhibit type B monoamine oxidase (MAO-B) in human brain synaptosomal mitochondria. By kinetic analysis, the inhibition of MAO-B activity by QUIN was competitive with the substrate, kynuramine. On the other hand, type A MAO (MAO-A) activity in human brain synaptosomal mitochondria and human placental mitochondria was not affected by QUIN. The selective inhibition of MAO-B by QUIN was confirmed using human liver mitochondria; only MAO-B was inhibited by QUIN and MAO-A was not inhibited. The inhibition was completely reversible. Among compounds structurally related to QUIN, 4-pyrimidine carboxaldehyde was the most potent substrate-competitive inhibitor of MAO-B, while 3-hydroxyanthranilic acid and xanthrenic acid, other metabolites of tryptophan, inhibited MAO non-competitively with the substrate. The inhibition of MAO-B by QUIN may be related to the causes of the neurotoxicity of QUIN.

Brain↗
PubMed1987

Inhibition of type A monoamine oxidase by 1-methyl-4-phenylpyridine.

1-Methyl-4-phenylpyridine (MPP+) is now confirmed to be one of the oxidative products of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by type B monoamine oxidase (MAO-B) and is considered to cause a parkinsonism-like syndrome. We studied the effect of MPP+ on type A monoamine oxidase (MAO-A) activity in mitochondria prepared from various sources. By kinetic analysis, MPP+ was found to inhibit MAO-A in competition with the substrate, kynuramine. The Ki value of MAO-A with MPP+ in human brain synaptosomal mitochondria (1.3 microM) was much lower than the Ki values of MAO-A in other organs. Among the MAO-A samples, MAO-A in intrasynaptosomal mitochondria from human brain was the most sensitive to MPP+. The Ki value of MAO-A with MPP+ in striatum (1.6 microM and 2.0 microM for MAO-A prepared from putamen and from caudate) was similar to the Ki value of MAO-A in synaptosomes from cortex. The difference in the Ki values of MPP+ for MAO-A from various sources was considered to be due to the difference in lipid components of mitochondria. The possible significance of the inhibition of MAO-A was discussed in terms of the etiology of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Inhibition of monoamine oxidase by 3,4-dihydroxyphenyl L-alanine and its analogues.

L-3,4-Dihydroxyphenylalanine (DOPA) was found to inhibit type A monoamine oxidase in human placental mitochondria. The inhibition proved to be noncompetitive with the substrate, kynuramine, and the inhibition was completely reversible. D-DOPA was found to inhibit monoamine oxidase in the same way, and the apparent Ki values of L- and D-DOPA were obtained to be 154 microM and 133 microM, respectively. L-alpha-Methyl-DOPA was found to inhibit the MAO activity competitively with the substrate, but studies with other analogues of DOPA revealed that the inhibition required an amino and a carboxyl group at alpha-position. The substitution of a hydroxy group at 3 or 4 position of catechol ring with a methoxy group was found to abolish the inhibition of the MAO activity. In addition to type A MAO in human liver and placental mitochondria, type B MAO in liver mitochondria was inhibited by L-DOPA, but type B MAO was less sensitive to L-DOPA. These results were discussed in terms of its possible regulation of the level of biogenic amines in the brain.

Dihydroxyphenylalanine↗
PubMed1987

Uptake of L-threo-dihydroxyphenylserine into human brain synaptosomes.

Out of four diastereoisomers of 3,4-dihydroxyphenylserine (DOPS), L-threo- and L-erythro-isomer were found to be taken up into human brain synaptosomes. The uptake of L-threo-DOPS was dependent on the temperature and sensitive to the metabolic inhibitors. The L-threo-DOPS uptake proved to be saturable and carrier-mediated transport with two different kinetic characteristics; a high-affinity and low-capacity and a low-affinity and high-capacity system. The apparent Km values of these two systems were obtained to be 28.6 microM and 2.47 mM, respectively. The high-affinity transport was inhibited by glycine, L-tyrosine, L-proline, L-serine, L-Dopa, L-tryptophan, and L-phenylalanine. The inhibition by L-tyrosine was competitive in regard to L-threo-DOPS. The L-threo-DOPS uptake was inhibited by 2,4-dinitrophenol, sodium cyanide and other uncouplers of oxidative phosphorylation and by ouabain, an inhibitor of Na+, K+-ATPase, indicating that the uptake is coupled to ATP hydrolysis. On the other hand, L-threo-DOPS uptake by the low-affinity system was not inhibited by metabolic inhibitors, indicating that it may be facilitated diffusion common to high concentrations of L-amino acids.

Amino Acids↗
PubMed1987

Ganglioside GM1 causes expression of type B monoamine oxidase in a rat clonal pheochromocytoma cell line, PC12h.

The effects of ganglioside supplementation of culture medium on monoamine oxidase (MAO) type A and B activities in a rat clonal pheochromocytoma cell line, PC12h, were examined. The MAO activity in PC12h cells proved to be mainly due to type A MAO, and type B MAO activity was negligible. After supplementation of the culture medium with ganglioside GM1, the PC12 cells were found to express type B MAO activity after 4 days of culture, and the amount of type B activity increased with the number of days of culture. After 3 weeks of culture in the presence of GM1, type B activity was about 10% of the total, whereas in control cells type B MAO activity was only about 0.6% of the total. By kinetic analyses of type A and B MAO in PC12h cells after 3 weeks of culture, the increase of type B MAO activity was found to be due to the increase in amount of type B MAO; the Km values were almost the same and only the Vmax values were increased in the cells supplemented with GM1. Among gangliosides tested GM1 was the most effective in causing expression of type B MAO activity, whereas nerve growth factor was not effective. These results suggest that GM1 and other gangliosides may be involved in the expression of type B MAO in nerve cells and in the regulation of levels of the biogenic amines in the brain.

Adrenal Gland Neoplasms↗
PubMed1987

Inhibition of monoamine oxidase by N-methylisoquinolinium ion.

N-Methylisoquinolinium ion (N-MIQ) has been found to inhibit the biosynthesis of catecholamines; it inhibited tyrosine hydroxylase activity in striatal tissue slices. In this article, the effects of N-MIQ and an analogue, N-methylquinolinium ion, on monoamine oxidase (MAO) activity were examined to see their effects on the catabolism of catecholamines. MAO-A in human placental mitochondria was strongly inhibited by N-MIQ in competition with the substrate. The apparent Ki value of N-MIQ was found to be 20.4 +/- 1.1 microM, whereas that of N-methylquinolinium ion was 54.6 +/- 4.5 microM. MAO-B in human brain synaptosomes and liver mitochondria was found to be inhibited by N-MIQ, but the inhibition proved to be noncompetitive. The inhibition of MAO-B by N-MIQ was completely reversible by dialysis of the incubation mixture. MAO-A in human brain and liver mitochondria was more sensitive to the inhibitor than MAO-B. By quantitative analysis of N-MIQ, using HPLC, it was found not to be catabolized by the incubation with mitochondria, suggesting that the inhibition was due to N-MIQ itself and not due to any metabolic product. The inhibition of MAO by N-MIQ is discussed in terms of its possible involvement of the etiology of parkinsonism.

Brain↗
PubMed1987

Effect of N-methyl-4-phenylpyridinium ion on monoamine oxidase in a clonal rat pheochromocytoma cell line, PC12h.

The effects of the neurotoxin N-methyl-4-phenylpyridinium ion (MPP+) on the enzymes involved in synthesis and catabolism of catecholamines were examined using a clonal rat pheochromocytoma cell line, PC12h, as a model of dopaminergic neurons. MPP+ added in the culture medium was found to be accumulated in PC12h cells after 30-min incubation. Monoamine oxidase (MAO) activity in PC12h cells was inhibited by MPP+ in a dose-dependent way from 10 nM to 10 microM, but concentrations of MPP+ higher than 100 microM were found to increase the MAO activity. At the lower concentrations MPP+ inhibited MAO noncompetitively with respect to the substrate, kynuramine, and at the higher concentrations it increased both the Km and the Vmax values of MAO toward the substrate. On the other hand, tyrosine hydroxylase activity and the dopamine concentrations in PC12 cells were not changed by incubation with MPP+ for 30 min, 60 min, or 24 h.

1-Methyl-4-phenylpyridinium↗
PubMed1986

Pancreas cancer associated antigen from normal colonic mucosa (PCAAc) assayed with monoclonal antibody.

We prepared monoclonal antibodies against pancreatic cancer associated antigen (PCAA) from normal colonic mucosa (PCAAc) and prepared an assay system to detect the circulating PCAAc in sera. 200 patients with cancer including 85 pancreatic cancer and benign disease were compared with 40 normal healthy individuals. Diagnostic rate of pancreatic cancer was 64/85 (75%) but other malignancy also showed elevated PCAAc: 18/19 (94.7%) of hepatoma and 19/37 (51.4%) of gastric cancer. In pancreatitis, 8/17 (47.1%) showed elevated PCAAc. Compared with our previous reports of PCAA assay, these results indicated that diagnostic sensitivity of pancreatic cancer was increased but specificity of it was decreased.

Antibodies, Monoclonal↗
PubMed1986

Inhibition of monoamine oxidase by 3,4-dihydroxyphenylserine.

The effects of diastereomers of 3,4-dihydroxyphenylserine (DOPS) on the enzyme activity of monoamine oxidase (MAO) in human placenta and liver mitochondria were examined. Both L- and D-threo-DOPS were found to inhibit MAO-A in human placental mitochondria in competition with the substrate, and the Ki values for L- and D-threo-DOPS obtained were 68.3 and 125 microM, respectively. The inhibitory effect of L-threo-DOPS on both MAO-A and -B activity was confirmed in human liver mitochondria, and MAO-A was found to be more sensitive to the inhibitor. Other isomers of DOPS, L- and D-erythro-DOPS, were found to inhibit MAO activity, but the inhibition was noncompetitive with the substrate. The inhibitory effects of DOPS isomers were not affected by the presence of NSD-1055, an inhibitor of aromatic L-amino acid decarboxylase, suggesting that the inhibition is the direct effect of DOPS, and not of norepinephrine produced by the decarboxylase.

Clorgyline↗