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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 415 records · Page 23Linked to original sources
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

Antiscorbutic effect of dehydro-L-ascorbic acid in vitamin C-deficient guinea pigs.

The antiscorbutic effect of dehydro-L-ascorbic acid (DAsA) was investigated in vitamin C-deficient guinea pigs. Male guinea pigs were fed vitamin C-deficient diets for 16 days to deplete body L-ascorbic acid (AsA) pools and then fed the deficient diet supplemented with DHA and/or AsA intraperitoneally for 14 days. During the repletion period, most of the animals injected with 0.5 mg DAsA/day developed scurvy, their body weights decreased and their mortality rate was higher than that of the other groups injected with 0.5 mg AsA/day or 5 mg DAsA/day. Injecting animals with 0.5 mg AsA/day resulted in the disappearance of the typical scorbutic symptoms and regaining of body weight. These data indicate that DAsA has considerably less antiscorbutic activity than AsA in vitamin C-deficient guinea pigs.

Adrenal Glands↗
PubMed1986

The tissue distribution of L-ascorbic acid and dehydro-L-ascorbic acid in the guinea pigs injected intravenously with dehydro-L-ascorbic acid.

The tissue distribution of L-ascorbic acid (AsA) and dehydro-L-ascorbic acid (DAsA) in guinea pigs injected with DAsA intravenously was examined using high-performance liquid chromatography. DAsA injected into guinea pigs fed normal diets containing AsA (control group) was readily taken into erythrocytes, and AsA contents of plasma and other tissues rapidly increased after DAsA injection. In animals fed vitamin C-deficient diets, DAsA was also detected in erythrocytes; however, the increase of AsA in their tissues was considerably less than that of control group. From these results, it was suggested that utilization of DAsA as AsA in vitamin C-deficient guinea pigs was less than that of control animals, and the reduction mechanism of DAsA to AsA in vitamin C-deficient guinea pigs may have differed from that of control groups.

Administration, Oral↗
PubMed1986

Metabolic fate of the new cardiotonic denopamine in animals. 1st communication: absorption, distribution and excretion in the rat, rabbit and dog.

Absorption, distribution and excretion of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino] ethanol (denopamine, TA-064) a new positive inotropic agent, were studied after oral and intravenous administration of 3H- or 14C-denopamine (5 mg/kg) to different animal species. After oral administration to rats, rabbits and dogs, the time to attain the peak and the maximum concentration of the plasma levels of radioactivity were about 15 min, 4 micrograms eq./ml in rats, 15-45 min, 8 micrograms eq./ml in rabbits and 2-4 h, 2 micrograms eq./ml in dogs, respectively. The plasma denopamine levels in dogs reached the peak (0.34 microgram/ml) at 0.5-3 h after administration, and thereafter gradually decreased with half-lives of 1.6-3.1 h. Following oral administration to rats, the amounts remaining of the parent compound in the digestive tract at 0.5 and 3 h after administration were about 27 and 2% of the dose administered, respectively. This indicated that the compound was rapidly and almost completely absorbed from the intestinal tract. When 3H-denopamine was orally administered to rats, cumulative excretion of radioactivity in the urine and feces within 24 h were about 60 and 32% of the dose, respectively. Almost 100% of the dose were recovered from the urine and feces within 120 h. About 50% of the dose administered were excreted in the bile within 24 h. The occurrence of enterohepatic circulation was indicated in rats. Distribution of radioactivity was investigated in rats by means of whole body autoradiography and the tracer technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Metabolic fate of the new cardiotonic denopamine in animals. 2nd communication: tissue accumulation in the rat after consecutive oral administration of 14C-denopamine.

Accumulation characteristics of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064) in organs and tissues were investigated after oral administration of 14C-denopamine to rats once a day (5 mg/kg/d) for 1, 6 and 10 days. The levels of radioactivity in each organ and tissue were measured at various time intervals after the final dose. The levels of radioactivity at 15 min after administration were generally higher in the consecutive-dose groups than in the single-dose group. However, the levels were equilibrated within 6 days of administration. Radioactivity at 24 h after administration decreased to about the detection limit in each group. In addition, half-lives of disappearance of radioactivity from the body were not significantly affected by the consecutive doses. About 100% of the dose was recovered from the urine and feces during consecutive administration periods. Consequently, it was considered that the drug hardly showed retention and accumulation characteristics in the body.

Administration, Oral↗
PubMed1986

Metabolic fate of the new cardiotonic denopamine in animals. 3rd communication: placental transfer and excretion into milk in the rat.

3H-labelled (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064) was administered orally to pregnant rats at a dose of 5 or 60 mg/kg on the 14th or 20th day of pregnancy. Irrespective of the doses and the stages of pregnancy, radioactivity in the fetus reached a peak at 30 min after administration, being 1/7 to 1/25 of the maternal plasma levels. Total radioactivity in each fetus at 30 min was estimated to be only about 0.002 to 0.06% of the dose. Disappearance of radioactivity from the fetus, uterus and amniotic fluid was slightly slower than that from the maternal plasma. After 3H-denopamine (5 mg/kg) was orally administered to lactating rats on the 12th day after delivery, radioactivity in milk was generally lower than in the blood of the dams, and time to the peak levels in milk tended to delay as compared with that in the blood. The levels of radioactivity in the blood of the sucklings, nursed by their dams, at 1 h after nursing were about 1/30 of the maternal blood levels, showing a slight transfer of the drug and/or its metabolites via milk. At 24 h after administration, radioactivity levels in the sucklings decreased to near the detection limit. The results of whole body autoradiography were generally consistent with the quantitative data on the placental transfer and excretion into milk.

Animals↗
PubMed1986

Metabolic fate of the new cardiotonic denopamine in animals. 4th communication: effects of coadministered drugs on the plasma concentration and metabolism of denopamine in dogs.

Effect of coadministered drugs on plasma level and metabolism of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064), a new, orally active, cardiotonic agent, were studied in dogs. Plasma levels of denopamine and urinary excretion of denopamine and its main metabolites were determined after oral administration of denopamine with or without digoxin, furosemide and isosorbide dinitrate. Mean plasma levels of denopamine were slightly lower when denopamine was given with the coadministered drugs than when given alone, but the difference was not statistically significant. No significant differences were also found between the areas under the plasma concentration curve (110 vs. 127 ng/ml X h, with and without the coadministered drugs, respectively), peak plasma concentrations (32.4 vs. 39.6 ng/ml), times to peak concentration (1.2 vs. 1.0 h) and plasma half-lives (2.2 vs. 2.0 h), respectively. In addition, the urinary excretion of denopamine and its main metabolites was not affected by the coadministered drugs.

Animals↗
PubMed1986

Penetration into and elimination from the cerebrospinal fluid of diltiazem, a calcium antagonist, in anesthetized rabbits.

Penetration into and elimination from the cerebrospinal fluid (CSF) of diltiazem were studied following intravenous (i.v.) or intra-cisternal (i.c.) administration of 14C-diltiazem to anesthetized rabbits. 14C-Diltiazem rapidly penetrated into the CSF through the blood-CSF barrier after i.v. injection (1 mg/kg). A CSF level of the radioactivity attained the peak (0.13 microgram eq./ml) 5 min after i.v. injection and declined bi-exponentially with rapid initial half-life of 3.8 min (5-15 min) and second half-life of 2.7 h (15 min-8 h). A CSF/plasma ratio was 0.05-0.2 throughout the observation period. After i.c. administration (100 micrograms/body), the CSF level of the radioactivity decreased with a half-life of 7.5 min up to 1 h. The CSF level was maintained above 10(-7) mol/l until 2-3 h. Elimination half-life of 14C-diltiazem after i.c. injection was much more similar to that of 3H2O than 14C-inulin, indicating that the main elimination route of this compound from the CSF is diffusion into the brain, followed by rapid diffusion into the cerebral capillary, rather than filtration from the sub-arachnoid villi. An autoradiographic investigation supported the above route of elimination.

Animals↗
PubMed1985

Respiratory reflexes in an isolated brainstem-lung preparation of the newborn rat: possible involvement of gamma-aminobutyric acid and glycine.

An isolated brainstem-lung preparation of the newborn rat was developed for a pharmacological study on the respiratory reflexes in vitro. Spontaneous periodic depolarizations of the ventral roots (C4-C5) were observed at a frequency of 5-15/min and regarded as the respiratory activity. This activity was transiently inhibited when the lungs were inflated by gas pressure applied to the trachea. The inhibitory response of the respiratory rhythm was markedly depressed by the application of bicuculline or strychnine to the brainstem. These results suggest that gamma-aminobutyric acid and/or glycine may be neurotransmitters in the brainstem which cause the inhibitory respiratory reflex.

Animals↗
PubMed1985

Ability of various alkylating agents to induce adaptive and SOS responses: a study with lacZ fusion.

We used alkA'-lacZ' and umuC'-lacZ' fused genes and determined the ability of various alkylating agents to induce adaptive and SOS responses. The degree of induction of expression of these genes was quantitatively measured by a simple colorimetric assay of beta-galactosidase activity. SN1 type methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, were more effective inducers for the alkA than for the umuC system, while SN1 type ethylating agents, such as N-ethyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea, were more potent inducers for the umuC than for the alkA system. Similar but less striking effects on the two systems were obtained with SN2 type alkylating agents.

Alkylating Agents↗
PubMed1985

The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord.

In order to reveal the spinal reflexes involving the transmitter action of substance P (SP), the effects of capsaicin and an SP antagonist on the isolated spinal cord of the neonatal rat studied. When a single shock stimulus was given to a dorsal root (L3-L5) or a sciatic nerve, depolarizing responses of various time courses were recorded extracellularly from both ipsi- and contra-lateral ventral roots of the corresponding segments. The reflex response recorded from the contralateral ventral root consisted of fast and slow components, which will be referred to as contralateral fast and slow ventral root potentials (v.r.ps). The latter contralateral slow v.r.p. had a time-to-peak of 2-5 s and lasted 10-30 s. The threshold for the contralateral slow v.r.p. was about two times higher than that for the monosynaptic reflex, and it coincided with the threshold for activating the slow-conducting afferent fibres. The contralateral slow v.r.p. was abolished after the spinal cord was treated with capsaicin (1 microM for 30 min) in vitro. The contralateral slow v.r.p. was absent in the spinal cord derived from 4-day-old rats that had received capsaicin (50 mg kg-1, s.c.) on the 2nd day of life. The contralateral fast v.r.p. and other reflexes of fast time courses remained unaltered after treatment with capsaicin in vitro or in vivo. Administration of an SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9 Leu11]-SP in concentrations of 5-16 microM depressed the contralateral slow v.r.p., but did not affect the monosynaptic reflex, the dorsal root potential and the contralateral fast v.r.p. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (5 microM) markedly depressed the SP-induced depolarizing response recorded from the ventral root whereas the responses to noradrenaline, 5-hydroxytryptamine, neurotensin and thyrotrophin releasing hormone (TRH) were unaffected by the SP antagonist. The response of the ventral root to acetylcholine was slightly depressed by the antagonist. The SP antagonist at 5-10 microM did not exert any agonist action on the motoneurones. The present results in conjunction with those of previous studies support the hypothesis that SP released from certain primary afferent fibres acts as a neurotransmitter, producing in dorsal horn neurones slow excitatory postsynaptic potentials which lead to the generation of the contralateral slow v.r.p.

Animals↗
PubMed1985

Blockade of slow excitatory post-synaptic potential by substance P antagonists in guinea-pig sympathetic ganglia.

The effects of three substance P (SP) antagonists on the inferior mesenteric ganglion of the guinea-pig were studied using intracellular recording techniques, and the possible role of SP as a transmitter for the non-cholinergic slow excitatory post-synaptic potential (e.p.s.p.) was examined. The SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP, exerted a depolarizing action on the ganglion cells when applied by perfusion at a concentration of 3-16 microM or by pressure ejection from a micropipette. This depolarizing action is probably due to a release of endogenous histamine because it was abolished by treatment with a histamine antagonist, mepyramine (1-3 microM), or by a repeated application of the antagonist. When applied by pressure ejection, SP at 0.5-1 microM depolarized the ganglion cells. In the presence of mepyramine, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP suppressed the SP-induced depolarization by 41% at a concentration of 8 microM and by 75% at 16 microM. By contrast the SP antagonist did not affect the depolarizing action of angiotensin II on the ganglion cells. The non-cholinergic slow e.p.s.p. evoked in the ganglion cells by repetitive stimulation of the lumbar splanchnic nerves was suppressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP at 8 or 16 microM. The degrees of suppression of both the non-cholinergic slow e.p.s.p. and the SP-induced depolarization by the SP antagonist were approximately equal. The cholinergic fast e.p.s.p. evoked by preganglionic nerve stimulation was not affected by the SP antagonist. [D-Pro2, D-Trp7,9]SP exhibited the properties of an SP antagonist similar to, but slightly weaker than [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP. [D-Pro2, D-Phe7, D-Trp9] at a concentration of 16 microM had a depolarizing action on the ganglion cells, which was not blocked by mepyramine. The peptide exerted hardly any antagonistic action against the SP-induced depolarization of the ganglion cells. Stimulation of the other preganglionic (intermesenteric) nerves and the post-ganglionic (colonic and hypogastric) nerves produced a non-cholinergic slow e.p.s.p. in the inferior mesenteric ganglion cells. The non-cholinergic slow e.p.s.p. evoked by both pre- and post-ganglionic nerve stimulation were depressed by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP to similar extents. The present results show that [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP and [D-Pro2, D-Trp7,9]SP can serve as specific SP antagonists in the inferior mesenteric ganglion of the guinea-pig.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗