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Biomedical subjects

R Ueno

Publications and source records attributed to R Ueno.

At least 73 records · Page 4Linked to original sources
PubMed1985

Changes of enzymes involved in prostaglandin metabolism and prostaglandin binding proteins in rat brain during development and aging.

In the developing rat brain, the enzymatic formation of prostaglandin D2 from prostaglandin H2 increased 60-fold from day 12 of gestation to birth. The activity still rose gradually to the highest level (90 nmol/min/g wet tissue) at day 7 after birth. The activities of prostaglandin E2 and F2 alpha synthetases in rat brain were highest at gestational age 19 days (30 nmol/min/g wet tissue), respectively. The specific activity of NADP-dependent 15-hydroxy-prostaglandin D2 dehydrogenase in rat brain was highest at the earliest gestational age we examined (day 12 of gestation). The specific bindings of prostaglandin D2 and E2 to the crude mitochondrial fraction of rat brain were observed from day 16 of gestation and increased to day 7 after birth. Although the activities of the enzymes responsible for prostaglandin metabolism were unchanged postmaturationally, the maximal concentrations of the binding sites on the synaptic membrane for both prostaglandins D2 and E2 decreased with constant affinity to less than one-sixth with age from 1 week to 24 months after birth. These results indicate that prostaglandins may play important roles during maturation and aging in rat brain.

Aging↗
PubMed1985

Developmental changes in the activities of prostaglandin synthesizing enzymes in the digestive and immune systems of rat.

The developmental changes of prostaglandin (PG) synthesizing enzymes in the digestive system (stomach and small intestine) and the immune system (spleen and thymus) of rats were investigated. In all the digestive organs, the predominant PG produced from PGH2 changed at around 2 weeks after birth to another PG. Further, the predominant activities of PG synthesizing enzymes were different organ by organ in the digestive system. In the case of the immune system, only the activity of PGD2 synthesizing enzyme displayed a significant increase during development and the activities of other PG synthesizing enzymes remained insignificant throughout the development. These results suggest that PGs may play important roles during the development of each organ.

Aging↗
PubMed1984

Little sleep-promoting effect of three sleep substances diurnally infused in unrestrained rats.

Delta-sleep-inducing peptide (2.5 nmol), prostaglandin D2 (0.36 nmol) and uridine (10 pmol) were intraventricularly infused for 10 h at daytime in otherwise saline-infused freely moving male rats. In contrast to a nocturnal infusion which may result in marked sleep-promoting effects, such a diurnal infusion brought about almost no change in sleep parameters. It is postulated that the requirement of sleep in rats might be fully achieved at the environmental light period to cancel the effect of the exogenously administered sleep substances. It is proposed that an endogenous sleep substance should be characterized by a property not to cause excessive sleep at the time when sleep is physiologically saturated.

Animals↗
PubMed1984

Differential sleep-promoting effects of five sleep substances nocturnally infused in unrestrained rats.

Sleep-inducing and sleep-maintaining effects of five different putative sleep substances were compared by the same nocturnal 10-hr intracerebroventricular infusion technique in otherwise saline-infused, freely moving male rats. Delta-sleep-inducing peptide (2.5 nmol), which induces electroencephalogram delta (slow)-wave patterns, was rapidly effective in increasing both slow-wave sleep and paradoxical sleep but the effects were not long-lasting. Muramyl dipeptide (2 nmol) induced excessive slow-wave sleep in the middle of the infusion period, accompanying a simultaneous elevation of brain temperature. However, paradoxical sleep was not affected. Component B of sleep-promoting substance (2 brainstem equivalents), a partially purified extract from rats deprived of sleep for 24-hr, was markedly effective in inducing and maintaining both kinds of sleep. Prostaglandin D2 (0.36 nmol) was more effective in enhancing sleep at the later period of the infusion period. Uridine (10 pmol) caused a mild but long-lasting increase in sleep, especially in paradoxical sleep. Thus, each substance exhibited compound-specific sleep-modulating properties.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Prostaglandin D2, a cerebral sleep-inducing substance in rats.

We continuously monitored the circadian sleep patterns of unrestrained rats for more than 96 hr and infused various prostaglandins into their third ventricles for 10 hr to study the effects on inducing sleep. Prostaglandin D2 at 6 fmol/min had no effect on either slow wave sleep or paradoxical sleep. However, prostaglandin D2 at as little as 60 fmol/min caused a significant amount of excess slow wave sleep as compared with the control level during saline infusion. Paradoxical sleep was induced by prostaglandin D2 at doses greater than 600 fmol/min. Prostaglandin D2 (600 fmol/min) increased slow wave sleep by 33% and paradoxical sleep by 56%. Although prostaglandin F2 alpha (600 fmol/min) increased the amount of slow wave sleep, its activity was less than that of the same amount of prostaglandin D2. Prostaglandin E2 (600 fmol/min) had no effect on increasing the amounts of both slow wave sleep and paradoxical sleep. During the infusion of prostaglandin D2, rats were easily aroused by clap sound stimulation and their sleeping and waking postures remained normal. Further, their sleep was episodic, as observed in the physiological sleep of rats.

Animals↗
PubMed1982

Activation mechanism of prostaglandin endoperoxide synthetase by hemoproteins.

The mechanism of the activation of prostaglandin endoperoxide synthetase by hemeproteins was investigated using the enzyme purified from bovine seminal vesicle microsomes. At pH 8, the maximal enzyme activities with methemoglobin (2 microM), indoleamine 2,3-dioxygenase (2 microM), and metmyoglobin (2 microM) were 70%, 42%, and 15% of that with 1 microM hematin. Apomyoglobin and apohemoglobin inhibited the enzyme activities caused by hemoproteins as well as that caused by hematin. The inhibition was removed by the addition of excess hematin. The dissociation of heme from hemoproteins was demonstrated by trapping the free heme with human albumin or to a DE-52 column. The dissociation of heme from methemoglobin was facilitated by increasing concentrations of arachidonic acid. The amount of heme dissociated from hemoproteins (methemoglobin, metmyoglobin, and indoleamine 2,3-dioxygenase) in the presence of arachidonic acid correlated with their stimulatory effects on the prostaglandin endoperoxide synthetase activity. Horseradish peroxidase and beef liver catalase, the hemes of which were not dissociated in the presence of arachidonic acid, were ineffective in activating prostaglandin endoperoxide synthetase. Spectrophotometric titration of prostaglandin endoperoxide synthetase with hematin demonstrated that the enzyme bound hematin at the ratio of 1 mol/mol with an association constant of 0.6 x 10(8) M-1. From these results, we conclude that hemoproteins themselves are ineffective in activating prostaglandin endoperoxide synthetase and free hematin dissociated from the hemoproteins by the interaction of arachidonic acid is the activating factor for the enzyme.

Animals↗
PubMed1982

Regulation of cytochrome P450 activities in adrenocortical mitochondria from normal rats and human neoplastic tissues.

From our immunocytochemical studies, cytochrome P450scc and P45011 beta systems were localized on the matrix side of inner membrane of the mitochondria in the parenchymal cells of adrenal cortex. However, the degree of immunocytochemical staining varied from one mitochondrion to another within a single cell; some stained intensely along the entire inner membrane, some stained only along segments of the inner membrane, and some did not stain at all. The ratio of stained to unstained mitochondria was approximately unity in untreated rats, while stained mitochondria greatly increased upon ACTH administration suggesting that the population of cytochrome P450 system-containing mitochondria increased upon long-term ACTH action. By the combined use of flash photolysis and substrate difference spectroscopy, quantitative determination of substrate-bound and free forms of P450scc and P45011 beta in mitochondria became possible. Increases in total amounts of P450scc and cholesterol resulted from the long-term ACTH administration to rats. The ratio of cholesterol-bound P450scc to its free form was essentially unchanged under these conditions. On the other hand, amounts of P45011 beta were not increased significantly by long-term ACTH administration. The ratio of DOC-bound P45011 beta to the free form increased significantly, however, by long-term ACTH administration and also in the mitochondria from patients suffering from Cushing's syndrome.

Adrenal Cortex↗
PubMed1982

Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide.

The intraperitoneal administration of lipopolysaccharide from Salmonella typhimurium (1 mg/kg) caused a fall in the rat colonic temperature of about 2 degrees C at an ambient temperature of 22 +/- 3 degrees C. The hypothermia induced by the lipopolysaccharide was abated in a dose-dependent manner by the administration of indomethacin. Other inhibitors of prostaglandin synthetase such as aspirin, flufenamic acid, and phenylbutazone had effects similar to those of indomethacin. When various prostaglandins were injected intracerebroventricularly, only prostaglandin D2 caused a dose-dependent fall in the colonic temperature at doses between 1.2 and 6 nmol/kg. Microinjection of prostaglandin D2 into the preoptic area caused hypothermia of about 1 degree C. However, injection of prostaglandin D2 into the posterior hypothalamus had little effect on the colonic temperature. The hypothermia caused by prostaglandin D2 was not abated by the administration of indomethacin. The amount of prostaglandin D2 increased significantly in the preoptic/hypothalamic region of rat brain 1 hr after the intraperitoneal administration of the lipopolysaccharide, whereas such increase was not observed in rats pretreated with indomethacin. The in vitro incubation of the preoptic/hypothalamic slices with the lipopolysaccharide also increased the amount of prostaglandin D2. These results suggest that the intraperitoneal administration of the lipopolysaccharide induces the release of prostaglandin D2 in the preoptic/hypothalamic area of rat brain and that the latter compound is involved in the hypothermic response of rats to the lipopolysaccharide.

Animals↗
PubMed1982

Cytochrome P-45011 beta and P-450scc in adrenal cortex: zonal distribution and intramitochondrial localization by the horseradish peroxidase-labeled antibody method.

In an attempt to elucidate the regulation mechanism(s) of adrenocortical steroidogenesis, cytochrome P-450scc and cytochrome P-45011 beta were localized in bovine adrenal glands by the direct peroxidase-labeled antibody method. At the light microscopic level, parenchymal cells of the zona fasciculata and the zona reticularis stained heavily for both cytochromes, while the parenchymal cells of zona glomerulosa stained lightly for both. At the electron microscopic level, these two cytochromes were associated with the matrix side of the inner mitochondrial membranes of parenchymal cells from all three zones of the adrenal cortex. The association of cytochrome P-450 with the inner mitochondrial membrane, in a manner similar to that previously reported for adrenodoxin and adrenodoxin reductase (F Mitani, Y Ishimura, S Izumi, K Watanabe, Acta Endocrinol 90:317, 1979), establishes that the steroid monooxygenase systems exist at this site. The degree of immunocytochemical staining within a single cell varied from one mitochondrion to another: some stained intensely along the entire inner membrane, including the cristae, some stained only along segments of the inner membrane, and some did not stain at all. This heterogeneity in staining was observed in mitochondria stained in situ as well as in isolated mitochondria. These findings suggest that there is a heterogeneity in steroidogenesis among mitochondria contained within a single cell of the adrenal cortex.

Adrenal Cortex↗