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T Obata

Publications and source records attributed to T Obata.

At least 199 records · Page 11Linked to original sources
PubMed1988

Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral cortex by triazolobenzodiazepines.

The effects of triazolobenzodiazepines on GABA-stimulated 36Cl- uptake by membrane vesicles from rat cerebral cortex were examined. Triazolam and alprazolam showed a significant enhancement of GABA-stimulated 36Cl- uptake at 0.01-10 microM. On the other hand, adinazolam showed a small enhancement at 0.1-1 microM followed by a significant inhibition of GABA-stimulated 36Cl- uptake at 100 microM. The enhancement of GABA-stimulated 36Cl- uptake by 1 microM alprazolam was antagonized by Ro15-1788, a benzodiazepine antagonist, but the inhibition of this response by 30 microM adinazolam was not antagonized by Ro15-1788. These results indicate that triazolobenzodiazepines enhanced GABA-stimulated 36Cl- uptake through benzodiazepine receptors. High concentrations of adinazolam inhibit GABA-stimulated 36Cl- uptake which may be due to the direct blockade of GABA-gated chloride channel.

Alprazolam↗
PubMed1988

New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships.

(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.

Animals↗
PubMed1988

Changes in amine oxidase in plasma of rats treated with hepatotoxins.

When allyl formate (AF) was administered to rats, the marked elevation of B-form MAO activity in plasma was found with beta-PEA as a substrate. In contrast, in the case of carbon tetrachloride (CCl4), A-form MAO activity elevated predominantly. The deaminations of 5-HT and beta-PEA in these plasma treated with AF or CCl4 were not inhibited completely by a high concentration of MAO inhibitor, deprenyl or clorgyline. These results indicate that there may be two or more distinct amine oxidases released from the liver and other organs in response to CCl4 or AF.

Animals↗
PubMed1988

Modulation of gamma-aminobutyric acid-stimulated chloride influx by bicycloorthocarboxylates, bicyclophosphorus esters, polychlorocycloalkanes and other cage convulsants.

gamma-Aminobutyric acid (GABA) stimulated 36Cl- influx into membrane vesicles from rat cerebral cortex at 3 to 300 microM in a concentration-dependent manner with near maximum response at 100 microM. Inhibitory potencies for this GABA (100 microM)-dependent 36Cl- uptake were determined for 16 cage convulsants including 10 bicycloorthocarboxylates and 3 bicyclophosphorus esters and for 8 polychlorocycloalkane insecticides. Inhibition by derivatives of t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) depended on the substituents at both positions 1 and positions 4. Among them, the 4-cyano-phenyl analog of TBOB was the most potent inhibitor with an IC50 value of 40 nM. Other cage convulsants such as picrotoxinin, tetramethylenedisulfotetramine and p-chlorophenylsilatrane were less potent than TBOB and TBPS. The potencies of bicycloorthocarboxylates, bicyclophosphorus esters and other cage convulsants in inhibiting GABA-stimulated 36Cl- uptake by rat cerebral cortex were significantly correlated with those in inhibiting [35S]TBPS binding to the human and mouse brain receptors (r = 0.96, P less than .01). There also was a significant correlation between the potencies of the polychlorocycloalkanes examined in inhibiting GABA-stimulated 36Cl- uptake and [35S]TBPS binding to the mouse brain receptor (r = 0.94, P less than .01). In these correlations, the polychlorocycloalkanes appear to fall on a different line than that for the bicycloorthocarboxylates, bicyclophosphorus esters and other cage convulsants. Both the cage convulsants and the polychlorocycloalkanes are considered to act at convulsant sites coupled functionally to the GABA receptor chloride ionophore complex and thereby to modulate allosterically or directly the GABA-gated chloride channel leading to their toxic action.

Animals↗
PubMed1987

A cellular 3,3',5-triiodo-L-thyronine binding protein from a human carcinoma cell line. Purification and characterization.

A cellular binding protein for 3,3',5-triiodo-L-thyronine (T3) was solubilized with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) from A431 human epidermoid carcinoma cells. The binding activity is T3 specific. Analysis of the equilibrium binding data indicated that the binding protein has one class of binding sites for T3 with a Kd of (17 +/- 3) nM and Bmax of (1.8 +/- 0.6) pmol/50 micrograms of protein. The pH optimum for binding is 6.8. The T3 binding protein elutes from Sephadex G-200 in an included peak which has a Stokes radius of 40 A and sediments on glycerol gradients at 3.7 S. By affinity labeling with [3,5-125I]thyroxine a protein with a molecular weight of 58,000 was specifically labeled. Its isoelectric point was determined to be 7.1, which is different from the reported pIs of other thyroid hormone binding proteins. p58 was successively purified to apparent homogeneity by chromatography on Sephadex G-200, QAE-Sephadex, SP-Sephadex, and hydroxylapatite. Approximately 50 micrograms of purified protein was obtained from 2.5 X 10(9) cells with a yield of 1.1%. The purified protein retains its binding activity. The specific binding activity is enriched by approximately 1000-fold. With the availability of a purified protein with T3 binding activity, it becomes possible to study its cellular function.

Carcinoma, Squamous Cell↗
PubMed1987

Thyroid hormone action: induction of morphological changes and stimulation of cell growth in rat pituitary tumor GH3 cells.

The effects of thyroid hormones on morphology and growth were studied in rat pituitary tumor GH3 cells using medium containing serum depleted of thyroid hormones. T3 and T4 induce the cells to change from a flattened fibroblastic morphology to a rounded or spindle-shaped morphology. The induction in morphological changes is T3 and T4 specific and dose dependent. Thyronine and rT3 are ineffective in inducing morphological changes; the half-maximal effective concentrations for T3 and T4 are 0.3 and 2 nM, respectively. Concomitantly, T3 stimulates cell growth, as indicated by a 2-fold reduction in doubling time and a 2-fold increase in mitotic rate. The growth-stimulating effect has the same analog specificity and dose dependency as the morphological changes. The morphological changes could be potentially useful for evaluating the biological effects of T3 and its analogs and in studying the mechanism of thyroid hormone action.

Animals↗
PubMed1987

[Electrophoretic properties of mitochondrial monoamine oxidase in monkey liver].

Monkey liver monoamine oxidase (MAO) was predominantly the B-form enzyme from the observed differences in substrate specificities and differences in sensitivities to MAO inhibitors. It is known that a MAO inhibitor, pargyline, binds to MAO irreversibly in the molar ratio of 1:1. 3H-pargyline was used as a marker to determine the existence of MAO. The molecular weight of MAO in monkey liver mitochondria was investigated by SDS-polyacrylamide gel electrophoresis after solubilization of 3H-pargyline binding mitochondria with 6% sodium dodecyl sulphate (SDS). The subunit molecular weight was found to be 60,000. The molecular weight determined from the electrophoretic mobility on several concentrations of gels by disc gel electrophoresis in the absence of SDS was found to be 120,000. These results indicate that monkey liver mitochondrial MAO exists as a dimer. Isoelectric focusing of the enzyme after solubilization with 0.1% Triton X-100 and 0.75% Triton X-100 and 0.75% Lubrol showed that it had a pI value near 6.5. Similar pI values were obtained for enzyme preparations solubilized with 0.75% Triton X-100 after treatment with phospholipase A or methylethylketone. These results suggest that the pI value of MAO in monkey liver mitochondria does not depend on the properties of detergents used to solubilize the enzyme preparation.

Animals↗
PubMed1987

Evidence for existence of A and B form monoamine oxidase in mitochondria from dog platelets.

It is known that platelet MAO appears to behave more like the B-form enzyme than the A-form enzyme based on inhibitor sensitivity and substrate specificity. However, dog platelets showed a different substrate specificity such as high activity with 5-HT and beta-PEA as substrates. Moreover, dog platelet MAO was sensitive to the drugs clorgyline and harmaline with 5-HT as the substrate, while it was sensitive to the drug deprenyl with beta-PEA as the substrate. These results also indicate the existence of two forms of MAO in dog platelets unlike in other platelets such as those from humans. A-form MAO from dog platelets was more stable against heat treatment at 55 degrees C than A-form MAO from dog liver and brain. On the other hand, there was no difference in the heat resistance of the three enzymes with beta-PEA as the substrate. After digestion with trypsin at 37 degrees C for 30 min, it was found that MAO from dog platelets, brain and liver were mostly inhibited with 5-HT as the substrate. In contrast, MAO in brain and liver were inhibited about 10%, but platelet MAO was inhibited about 50% with beta-PEA as the substrate. From these results, it is considered that dog platelet MAO exists as the two forms of the enzyme and has different enzymic properties in comparison with those of MAO from dog liver and brain mitochondria.

Animals↗