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Biomedical subjects

C Inagaki

Publications and source records attributed to C Inagaki.

At least 91 records · Page 5Linked to original sources
PubMed1986

Characteristics of ethacrynic acid highly sensitive Mg2+-ATPase in microsomal fractions of the rat brain: functional molecular size, inhibition by SITS and stimulation by Cl-.

Studies were performed to characterize ethacrynic acid (EA) highly sensitive Mg2+-ATPase isolated from microsomal fractions of the rat brain. The functional molecular sizes of the EA highly sensitive and EA less sensitive Mg2+-ATPases, estimated by a radiation inactivation method, were 480 and 80 kDa, respectively. An anion transport inhibitor, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) inhibited the EA highly sensitive Mg2+-ATPase activity. The type of inhibition was uncompetitive with respect to ATP, and the inhibition was suppressed by anions such as Cl-, Br- and I-. Chloride ions stimulated enzyme activity with an increase in Vmax, but not in Km, for ATP. Anions tested also increased the enzyme activity in the following order of decreasing potency: Cl- greater than Br- greater than CH3COO- = I- greater than SO4(2-) = HCO3- greater than SO3(2-). These results suggest that EA highly sensitive Mg2+-ATPase is a relatively large molecule with anion-sensitive sites that affect the ATP hydrolyzing activity and the SITS binding capacity through anions, with Cl- being the most potent.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1986

Effect of erythorbic acid administration on ascorbic acid content in guinea pig tissues.

The effect of erythorbic acid (ErA) on ascorbic acid (AsA) content in the tissues of normal and AsA-deficient guinea pigs was studied. The animals were sacrificed at varying intervals during the experimental period, and the liver, adrenal glands, spleen and kidneys were removed. The amounts of AsA and ErA in the tissues were measured by HPLC. The content of AsA in the tissues of the animals administered both AsA and ErA was lower than that of the animals administered only AsA. But the disappearance rate of AsA from the tissues of the AsA-deficient animals was similar to that of the animals administered only ErA. The amount of AsA in the tissues of the animals administered both AsA and ErA during the repletion period was lower than that of the animals administered only AsA. These results suggest that ErA administration may affect the amount of AsA in the tissues by inhibiting its tissue uptake or its storage in the tissues, and not by accerelating the catabolism of AsA in the tissues.

Adrenal Glands↗
PubMed1986

Effects of amiloride on thermosensitivity of Chinese hamster cells under neutral and acidic pH.

The modifying effects of amiloride on the thermosensitivity of Chinese hamster V-79 cells were examined under both neutral (pH 7.3) and acidic (pH 6.6) conditions. Amiloride, a diuretic drug, is known to inhibit the Na+/H+ exchange activity. Under the extracellular pH of 7.3, amiloride (0.1-0.5 mM) enhanced the thermal cell killing powers of 42 degrees C hyperthermia with increasing concentration and exposure time of the drug. The age response of cells to 42 degrees C hyperthermia in the presence or absence of amiloride (0.5 mM) showed that amiloride sensitized cells to heat, especially those at G1-S boundary through middle S phases. On the other hand, the lowering of extracellular pH to 6.6 enhanced cell killing by 42 degrees C hyperthermia. When cells were exposed to 42 degrees C hyperthermia in the presence of amiloride at pH 6.6, cell survival decreased still more. The thermosensitizing effects of the lowered pH at 6.6 and amiloride appeared to be additive. From these results, it is suggested that the thermosensitization by amiloride is probably due, in part, to the inhibition of cellular Na+/H+ exchange activity. The present study proposes the possibility that amiloride may be useful as a hyperthermic sensitizer in a clinical treatment of cancer.

Amiloride↗
PubMed1985

Novel microsomal anion-sensitive Mg2+-ATPase activity in rat brain.

Ethacrynic acid (EA) highly sensitive Mg2+-ATPase activity was demonstrated in rat brain microsomes. Marker enzyme studies suggested that the EA highly sensitive Mg2+-ATPase activity originated mainly from plasma membranes, and possibly from synaptic vesicles. Oligomycin did not affect the EA highly sensitive Mg2+-ATPase activity. Sulfhydryl reagents, such as N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid), and anion transport inhibitors, such as 4-acetamide-4'-isothiocyanostilbene-2,2'-disulfonic acid, 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid and 2,4-dinitro-1-fluorobenzene, completely inhibited the EA highly sensitive Mg2+-ATPase activity with apparent Ki values at 5, 5, 8, 8 and 10 microM respectively. Treatment of microsomes with ethylenediaminetetraacetic acid and ammonium sulfate increased the EA highly sensitive Mg2+ and Na+,K+-ATPase activities, but not EA less sensitive Mg2+- or HCO3-ATPase activity, 2- to 3-fold that in crude microsomes. Relative substrate specificities of ATP much greater than GTP greater than ITP greater than UTP, CTP, a Km for ATP at 0.77 mM, and an optimal pH at pH 7.4 were observed. Among the anions tested (Cl-, Br-, F-, HCO3-, I-, SCN-, NO3-), EA highly sensitive Mg2+-ATPase activity was stimulated significantly by Cl- and reduced by NO3-. These data suggest that a novel, plasma membrane-located and anion-sensitive Mg2+-ATPase activity exists in the brain.

Adenosine Triphosphatases↗
PubMed1985

Effects of avermectin B1a and picrotoxin on striatal release of dopamine with reference to replacement of extracellular chloride with nitrate.

The present study was an attempt to elucidate the effects of avermectin B1a (AVM) and picrotoxin, an anion channel opener and blocker, respectively, on the release of endogenous dopamine from the slices of caudate nucleus of the rat, using a superfusion method in order to determine the interaction between these agents with the gamma-aminobutyric acid (GABA) receptor-anion channel complex. Avermectin (1.14-11.4 microM) reduced the Ca2+-dependent release of dopamine stimulated by 40 mM KCl without affecting the basal release of dopamine. In contrast, picrotoxin in doses larger than 20 microM facilitated the K+-stimulated release of dopamine. The inhibitory effect of avermectin was completely antagonized by 10 microM picrotoxin and 0.1 mM bicuculline; these doses of both agents did not change the K+-stimulated release of dopamine. Replacement of chloride (Cl-) in the superfusion medium with nitrate (NO3-) markedly facilitated the K+-stimulated release of dopamine and the increase was antagonized by verapamil (10 microM) and tetrodotoxin (1 microM). In the nitrate medium, avermectin reduced the K+-stimulated release of dopamine and the inhibitory effect was antagonized by bicuculline. However, picrotoxin up to 100 microM did not affect the K+-stimulated release of dopamine either in the presence or absence of bicuculline. These results suggest that the dopaminergic nerve terminals in the caudate nucleus receive inhibitory regulation through the facilitation of anion channels. This regulation is apparently altered depending on the main anion in the extracellular fluid.

Amino Acids↗
PubMed1985

Changes in microsomal Na+, K+-, Mg2+- and Ca2+-ATPase activities during proliferation of Chinese hamster V-79 and human HeLaS-3 cells.

Changes in microsomal Na+, K+-, Mg2+- and Ca2+-ATPase activities during cell proliferation were examined in Chinese hamster V-79 (V-79) cells (normal cells) and human HeLaS-3 (HeLaS-3) cells (malignant cells). For V-79 cells, the Mg2+-ATPase activity per cell (pmol Pi/h/cell) in the confluent phase was higher than that in the logarithmically growing (log) phase. The amount of microsomal protein per cell was also high in the confluent phase. Specific activities (mumol Pi/h/mg protein) of Na+, K+-, Mg2+- and Ca2+-ATPase were significantly lower in the confluent phase than in the log phase. For HeLaS-3 cells, an increase in Ca2+-ATPase activity per cell was observed. The amount of microsomal protein per cell did not change between the log and confluent phase. The specific activity of Ca2+-ATPase in the confluent phase was also markedly higher than in the log phase. The relation between changes in ATPase activities and cell proliferation is discussed.

Adenosine Triphosphatases↗
PubMed1985

[Complete remission obtained in refractory acute lymphocytic leukemia using high-dose cytosine arabinoside combined with low-dose L-asparaginase].

A 41-year-old male was diagnosed as acute lymphocytic leukemia (ALL) in November, 1982 and partial remission was obtained by a combination chemotherapy of LVP, DVP ABOP and VAMP. In January, 1983, peripheral blood showed an increasing number of leukemic cells and he was readmitted to our hospital. WBC count in the peripheral blood was 13,200/mm3 and an 82% ratio of leukemic cells was observed. Bone marrow aspiration showed a hypercellularity of 89.4% leukemic cells. High-dose Ara-C therapy was started at a dose of 3 g/m2 i.v. every 12 hours for 6 days. Leukemic cells in peripheral blood were rapidly decreased in number, and the nucleated cell count of bone marrow was also reduced after 3 weeks of treatment, however 95% of leukemic cells remained. Low-dose L-asparaginase was then supplemented at a dose of 2000 U for 3 days, and 2 months later complete remission was achieved. The side effects associated with this high-dose Ara-C therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose Ara-C combined with L-asparaginase should be added to the treatment of leukemia which is refractory to conventional chemotherapy.

Adult↗
PubMed1985

Effects of m-aminobenzamide on the response of Chinese hamster cells to hyperthermia and/or radiation.

The modifying effects of m-aminobenzamide (m-ABA), an inhibitor of poly(ADP-ribose) synthesis, on 42 degrees C hyperthermia- and/or radiation-induced cell killing were examined in Chinese hamster V-79 cells. When cells were exposed to 42 degrees C hyperthermia in combination with m-ABA (10 mM), cell survival decreased compared with that for 42 degrees C hyperthermia alone. Thermosensitizing effects of m-ABA changed with treatments in a decreasing order of during and after heating greater than during heating greater than after heating. Treatments with m-ABA during and/or after X irradiation enhanced radiation-induced cell killing. When cells were exposed to combined treatment with X irradiation, 42 degrees C hyperthermia (60 min), and m-ABA (24 hr), cell survival decreased markedly compared with that for X irradiation alone. However, with both X----42 degrees C and X----42 degrees C----m-ABA, the enhancement ratios (ER), designated as D0 ratio, were similar. These results suggest that the mechanisms of radiosensitization by m-ABA may be similar to those of 42 degrees C hyperthermia.

Animals↗
PubMed1984

Influence of histamine and prostaglandin on desensitization to neurotensin in rat blood pressure.

Triphasic depressor-pressor-depressor blood pressure responses to neurotensin (NT: 1.67 micrograms/kg i.v.) in anesthetized rats were not elicited when the second dose of NT was administered 20 min after the first injection. Pretreatment of animals with histamine markedly reduced the depressor response to NT, and vice versa. The triphasic blood pressure pattern remained unaffected with acetylcholine and serotonin treatment, and hypotensive effects of acetylcholine and serotonin were not modified by NT. Attenuation of depressor response induced by the second injection of NT was antagonized by pretreatment with prostaglandin synthesis inhibitors such as indomethacin, mefenamic acid and acetylsalicylic acid. These results suggest that histamine and prostaglandins play a role in the development of desensitization to NT in rat blood pressure.

Acetylcholine↗
PubMed1984

Effects of methylglyoxal bis(guanylhydrazone) on tumour and skin responses to hyperthermia in mice.

Effects of methylglyoxal bis(guanylhydrazone) (MGBG) on tumour and skin responses to hyperthermia (42 degrees C) were examined in C3H mice. MGBG (50 mg/kg) was administered intraperitoneally to mice 4 hours before hyperthermic treatment. The tumour (FM3A) growth time was elongated by an amount dependent on the exposure time of treatment at 42 degrees C (60, 90 and 120 min). Pre-treatment of mice with MGBG (50 mg/kg, i.p.) apparently further lengthened the tumour growth time after treatment at 42 degrees C. No significant damage of foot skin was caused by 42 degrees C hyperthermia. Pre-treatment with MGBG did not make the foot skin susceptible to the heating. From these findings, it can be considered that MGBG or related less-toxic compounds may have a clinical advantage for the mild (42 degrees C) hyperthermic treatment in cancer therapy.

Animals↗
PubMed1983

Release of histamine and adrenaline in vivo following intravenous administration of neurotensin.

Plasma histamine levels of rats anesthetized with pentobarbital sodium were significantly increased by intravenous administration of neurotensin (NT, 1 nmole/kg) with the maximum effect at 3 min, and a return to the initial levels in 20 min. Treatment of animals with compound 48/80 or disodium cromoglycate completely inhibited the elevation of histamine level by NT, however, treatment with reserpine or diphenhydramine and adrenalectomy did not affect the elevation. Plasma adrenaline levels increased transiently 1 min after NT injection, and adrenalectomy and treatment with compound 48/80 or diphenhydramine markedly reduced the elevation of adrenaline levels after NT injection. Plasma levels of noradrenaline were unchanged upon NT injection. These results provide direct evidence of the release of endogenous histamine and adrenaline following NT administration, and suggest the contribution of these amines to the NT-induced triphasic blood pressure responses (the first depressor, second pressor and third depressor responses) reported previously.

Animals↗
PubMed1983

Inhibitory effects of brotizolam, a new thienodiazepine, on limbic forebrain and neostriatal dopaminergic systems in vivo and in vitro.

Studies were performed to elucidate the effects of brotizolam, a newly synthesized thienodiazepine, chemically related to the benzodiazepines, on dopamine turnover in the limbic forebrain and neostriatum. Intraperitoneally administered brotizolam retarded the rate of alpha-methyl-p-tyrosine-induced depletion of dopamine in the olfactory tubercle (OT), nucleus accumbens (NA) and caudate nucleus (CN). Significant retardation was observed with brotizolam in doses ranging from 0.1-10 mg/kg in the olfactory tubercle, and from 1-10 mg/kg in the nucleus accumbens and caudate nucleus. These inhibitory effects of brotizolam were antagonized by bicuculline, a GABA antagonist, in all of the regions examined. Using slices of the olfactory tubercle, nucleus accumbens and caudate nucleus, the effects of brotizolam on dopaminergic nerve terminals were examined in vitro. Basal release of dopamine was not affected by brotizolam in concentrations up to 10(-6) M; however, K+-stimulated release of dopamine was significantly reduced by brotizolam at 10(-7) M or above. The reduction of K+-stimulated release of dopamine was antagonized by bicuculline, added in the superfusion medium. These data suggest that brotizolam inhibits the release of dopamine in the limbic forebrain and neostriatal systems probably through mechanisms including a facilitation of GABAergic action on dopaminergic nerve terminals.

Animals↗