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Biomedical subjects

N Matsuki

Publications and source records attributed to N Matsuki.

At least 127 records · Page 7Linked to original sources
PubMed1993

Electrophysiological properties of suncus (Suncus murinus) cardiac muscle.

1. Electrophysiological properties of cardiac muscle in Suncus murinus were compared with those of rat and guinea pig. 2. The resting potential and resting potassium permeability were smallest in suncus heart. 3. The action potential duration in suncus was also shortest, and effects of tetraethylammonium suggested that transient outward current is well developed in suncus. 4. Elicitation of slow response was very difficult in suncus, suggesting poor development of the calcium channel.

Action Potentials↗
PubMed1993

Emetic responses of Sorex unguiculatus.

We have shown previously that Suncus murinus, a species of the insectivore, can vomit in response to various emetogenic stimuli. In the present study we investigated whether or not Sorex unguiculatus, which belongs to different subfamily (Soricinae) of insectivore, vomits in response to emetogenic drugs. Subcutaneous injection of veratrine and oral administration of copper sulfate caused emesis in the animal. Histological study showed that bilateral structure of the area postrema was not important for the emetic reflex. Therefore, the capability of emesis may be common to the family of soricidae of the insectivore, and the Sorex unguiculatus is the smallest known mammal which can vomit.

Animals↗
PubMed1992

Effects of calcitonin gene-related peptide (CGRP) on Ca(2+)-channel current of isolated smooth muscle cells from rat vas deferens.

Effects of calcitonin gene-related peptide (CGRP), a putative non-adrenergic non-cholinergic neutrotransmitter on the electrical properties of the cell membrane, were investigated in enzymically dispersed smooth muscle cells from rat vas deferens. Under current clamp conditions, CGRP (up to 10(-7) M) did not induce significant changes in membrane potentials or input resistance in the resting state. The configurations of action potentials elicited by depolarizing current pulses were also unaffected, except that a prolongation of the duration of the action potentials by a high dose (10(-7) M) of CGRP was observed in some of the cells. Under whole cell voltage clamp conditions, the transient and sustained K+ currents, activated by depolarizing voltage-steps, were apparently decreased in the presence of 10(-9) to 10(-7) M CGRP. The peptide increased the voltage-gated Ca2+ current in cells loaded with 145 mM Cs+ solution in order to block the K+ currents. The voltage-dependency of the peak Ca2+ current was not changed by CGRP. Ba2+ (10.8 mM) was used as a charge carrier for the Ca(2+)-channel current to clarify further the effects of CGRP on the properties of the current. CGRP (10(-8) M) delayed the inactivation time course of the Ca(2+)-channel current and slowed the recovery from inactivation. The peptide did not affect the steady-state inactivation measured by changing the holding potential. The Ca(2+)-channel current in the presence of CGRP was suppressed by nicardipine (10(-6) M) to the same extent as the current under control conditions. The results suggest that CGRP modifies the L-type Ca2+ channel in smooth muscle cells.

Animals↗
PubMed1992

Cisplatin-induced emesis in Suncus murinus.

Emetic responses to cisplatin and participation of vagal innervation in emesis were studied in suncus. Intraperitoneal and intravenous administration of cisplatin caused dose-dependent emesis. ED50 values, latencies and frequencies were not significantly different between the two administrations. Cis-diaqodiammineplatinum (DAP), an active metabolite of cisplatin, also induced emesis, but with significantly shorter latency. Vagotomy completely abolished both types of vomiting. These results suggest that cisplatin is metabolized to DAP that subsequently causes emesis through stimulation of the vagus afferent.

Animals↗
PubMed1992

Postsynaptic potentiation of neurotransmission by neurokinin A in rat vas deferens.

Effects of neurokinin A (NKA) on sympathetic neurotransmission were studied in rat vas deferens. Although neither prazosin, an alpha 1-adrenoceptor blocker, nor alpha, beta-methylene adenosine triphosphate, a P2-purinoceptor blocker, inhibited the NKA-induced contractions in the epididymal site, high concentration of NKA-induced contractions in the prostatic site were slightly decreased by either of the two blockers. Treatment with guanethidine, which prevents the release of sympathetic transmitters from presynaptic nerve endings, also had no effect on NKA-induced contractions in either site. To investigate the effects of NKA on the adrenergic and purinergic neurotransmission in more detail, we measured transmitter release by using [3H]norepinephrine or [14C]adenosine. Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by electrical stimulation in the epididymal site, which may be originated from smooth muscle. In the prostatic site, contractions induced by electrical stimulation were enhanced in spite of no increase in 3H or 14C efflux. These results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site, and 3) NKA modulates the neurotransmissions.

Animals↗
PubMed1991

Efficient Ca2+ mobilization induced by neurokinin A in rat vas deferens.

Although both neurokinin A (NKA) and norepinephrine (NE) induced similar maximal contractions in the epididymal and the prostatic site of vas deferens, NKA affected sensitivity more potently than did NE in both sites. The NKA-induced contractions were more strongly inhibited by nicardipine, a dihydropyridine Ca2+ entry blocker, or by elimination of extracellular Ca2+ (Cao2+) in both sites. However, ryanodine, which interferes with the release of intracellular Ca2+ (Cai2+), abolished the contractions caused by NKA in the prostatic site whereas it had no effect in the epididymal site. These results suggest that NKA-induced contraction utilizes both Cai2+ and Cao2+ in the prostatic site but mobilizes only Cao2+ in the epididymal site. Cai2+ concentration [( Ca2+]i) was measured directly with a Ca(2+)-sensitive fluorescent dye, fura-2. In the epididymal site NKA induced contractions with smaller increase in [Ca2+]i compared to that necessary for NE-induced contractions. These results suggest that NKA utilizes Ca2+ more efficiently than does NE and plays a role as a neuromodulator in rat vas deferens.

Animals↗
PubMed1991

5-Hydroxytryptamine is emetogenic in the house musk shrew, Suncus murinus.

The emetic effects of 5-hydroxytryptamine (5-HT) and 5-HT3 receptor agonists were investigated in the house musk shrew, Suncus murinus. 5-Hydroxytryptamine (5-HT; i.p., i.v., s.c.) and 2-methyl-5-HT (2-Me-5-HT; i.p.) but not 5-hydroxyindoleacetic acid (i.p.) or 5-methoxytryptamine (i.p.) induced emesis with very short latency. Tropisetron (ICS 205-930, a 5-HT3 receptor antagonist, s.c.) blocked the emesis induced by 5-HT (10 mg/kg, i.p.) and 2-Me-5-HT (5 mg/kg, i.p.) with respective ID50 values of 7.8 and 70.9 micrograms/kg. Pindolol (5-HT1 receptor antagonist) and ketanserin (5-HT2 receptor antagonist) were about 100 times less potent than tropisetron. The emesis induced by 5-HT was prevented by surgical vagotomy but not by pretreatment with a combination of atropine (0.1 mg/kg, s.c.) and hexamethonium (10 mg/kg, s.c.). These results clearly indicate that 5-HT is emetogenic probably through a stimulation of peripheral 5-HT3 receptors.

5-Methoxytryptamine↗
PubMed1991

Deficiency of apolipoprotein B synthesis in Suncus murinus.

We reported previously that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food. In this study, we focused on lipoprotein and apolipoprotein secretion from the liver. The study of lipoproteins from this animal revealed that small amounts of lipoproteins with apolipoprotein (apo) E but without apo B were observed in the fraction of density less than 1.08 g/ml. In order to learn whether apo B is synthesized by the liver or not, isolated suncus livers were perfused with an addition of [35S]methionine. Small amounts of radioactivity were observed in apo E of VLDL, and fairly large amounts in apo E and A-I in the fraction of LDL + HDL, suggesting that VLDL was secreted with apo E but not with apo B from the liver. Northern blot analysis with use of rat apo B cDNA revealed a weak signal of hybridized rat apo B cDNA between 15 kb and 9 kb in the suncus liver and intestinal mucosa; this is almost the same size as rat apo B mRNA. This finding suggests the presence of apo B mRNA in the suncus. In conclusion, apo B is not secreted from the suncus liver, owing to a defect in intracellular post-transcriptional processing or to ineffective transcription. This might be one of the reasons for fatty deposits in the suncus liver. Suncus may be a candidate for an animal model of abetalipoproteinemia as well as fatty liver due to a defect of apo B synthesis.

Animals↗
PubMed1991

Selective blockade of cytotoxic drug-induced emesis by 5-HT3 receptor antagonists in Suncus murinus.

Antiemetic effects of serotonin 5-HT3 receptor antagonists (ICS205-930, zacopride, BRL43694, GR38032F) were investigated in Suncus murinus. Veratrine, nicotine, copper sulfate, cisplatin, cyclophosphamide and motion sickness were used as emetic stimuli. Serotonin 5-HT3 receptor antagonists did not inhibit emetic responses to veratrine, nicotine, copper sulfate and motion sickness. However, cisplatin- and cyclophosphamide-induced emesis was strongly blocked by them. Both subcutaneous and intravenous injections of 5-HT3 antagonists were effective. Serotonin 5-HT1 and 5-HT2 receptor antagonists were less effective. These results clearly indicate that a 5-HT3 receptor-mediated mechanism(s) is involved in the emesis caused by cancer chemotherapeutic agents and that 5-HT3 receptor antagonists are very effective as prophylactic drugs.

Animals↗
PubMed1991

Exercise-induced phospholipid degradation in the equine skeletal muscle and erythrocytes.

To understand the pathogenesis of equine exercise-induced myopathies and hemolysis, changes of phospholipid peroxidation products in the equine middle gluteal muscle and erythrocytes following the high-speed treadmill exercise were studied. In the skeletal muscle, the peroxidized phosphatidylethanolamine (PE) were increased at 24 hours after the exercise. The malondialdehydes (MDAs) were also increased as the protein-bound MDAs following exercise. In the erythrocytes, the peroxidized PE were significantly decreased at 24 hours after the exercise. The protein-bound MDAs were significantly increased at 5 min after the exercise and returned to the base values at 24 hours after the exercise. These findings indicate that the PE is more susceptible to in vivo oxidative effects than the other phospholipid classes, and the accumulation of the protein-bound MDAs is considered to play some cytotoxic roles in the equine skeletal muscle and erythrocytes following exercise.

Animals↗
PubMed1991

Role of histamine in motion sickness in Suncus murinus.

The levels of histamine (HA) and tele-methylhistamine (t-MH) were determined in five brain regions of Suncus murinus (suncus) and the effects of motion stimulus or drugs influencing the turnover of these amines were studied to elucidate the role of histamine in motion sickness. Shaking the animals for 2 min increased HA contents in telencephalon and diencephalon without significantly changing the t-MH levels. alpha-Fluoromethylhistidine (alpha-FMH), which is presumed to deplete the neuronal HA, tended to raise the HA levels. alpha-FMH slightly alleviated the vomiting response to motion stimulus and suppressed the HA increase in diencephalon caused by shaking. Compound 48/80, which releases HA from mast cells, did not alter the control HA levels, but effectively prevented the motion sickness and completely suppressed the motion-induced rises in HA levels. These results provide further evidence that brain HA plays an important role in the development of motion sickness.

Animals↗
PubMed1991

[Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin].

Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Induction of fatty liver by fasting in suncus.

We found that a fatty liver was easily induced in a novel experimental animal, Suncus murinus (suncus), by withholding food. Hepatic triglyceride content increased linearly for up to 24 h after fasting in these animals. Serum levels of neutral lipids are very low in the fed state compared with those in rats, and decreased significantly after 24 h fasting. On the other hand, serum free fatty acids, which are at the same level in fed animals as in rats, increased threefold in the fasting suncus. In order to learn whether the fatty liver induced by fasting is an unusual physiological state or a pathological on-going state in suncus, they were refed after 24 h fasting. Refeeding resulted in a decrease in hepatic triglyceride content to the level of fed animals. Serum lipid levels, which decreased with fasting, returned to those of fed animals. This evidence indicates that hepatic lipid secretion is impaired even in a physiological state to some extent and that starvation causes increasing influx of free fatty acid to the liver, which might be followed by esterification and result in triglyceride accumulation in the liver. In conclusion, hepatic lipid and lipoprotein metabolism is unique to the suncus, which is a useful animal model for the study of intra-hepatic lipid transport.

Animals↗
PubMed1990

Deficiency of beta-adrenoceptor-mediated relaxation in suncus trachea.

Characteristics of beta-adrenoceptor in the tracheal smooth muscle of Suncus murinus (suncus) were studied in comparison with those of rats and guinea pigs. Isoproterenol induced concentration-dependent relaxation of suncus trachea. However, the maximal relaxation was very small, and about 1000 times higher concentration was necessary compared to the case of the guinea pig. The order of the sensitivity to isoproterenol and the maximal relaxation was guinea pig much greater than rat greater than suncus. Tracheae from younger suncus were more sensitive to isoproterenol, but the maximal relaxation was not significantly different from the results using adult animals. Forskolin, a direct activator of adenylate cyclase, relaxed tracheae to similar extents in the three species. Though the affinity of specific [3H]dihydroalprenolol binding was not significantly different, the maximal number of binding sites was in the order of rat greater than guinea pig greater than suncus. However, the differences in density of the binding among the three species were not as great as differences in isoproterenol-induced relaxation. These results suggest that 1) beta-adrenoceptor-mediated relaxation of tracheal smooth muscle is not well-developed in the suncus and 2) the deficient relaxation is probably caused by insufficient coupling between adrenoceptors and adenylate cyclase.

Animals↗
PubMed1990

Changes in intracellular free Ca2+ concentration by activation of alpha-adrenoceptors in rat tail artery.

Changes in intracellular free Ca2+ concentration ([Ca2+]i) by activation of alpha 1- and alpha 2-adrenoceptors were microfluorometrically measured in rat tail arteries loaded with the Ca2(+)-sensitive fluorescent dye fura-2. Under the normal condition (1.8 mM Ca2+), stimulation with the selective alpha 1-adrenoceptor agonist phenylephrine very rapidly raised [Ca2+]i to the peak concentration, plateauing at this level, whereas the stimulation with the selective alpha 2-adrenoceptor agonist UK-14,304 gradually increased [Ca2+]i. In Ca2(+)-free solution, the stimulation of alpha 1-adrenoceptors caused a transient increase in [Ca2+]i, whereas the stimulation of alpha 2-adrenoceptors had no effect. These results directly prove that alpha 1-adrenoceptor activation induces both the release of intracellular Ca2+ and the influx of extracellular Ca2+, whereas activation of alpha 2-adrenoceptors evokes only the influx of extracellular Ca2+. Plotting the increase in [Ca2+]i against the developed contraction revealed that it was always linearly related regardless of the type of alpha-adrenoceptor stimulated. Therefore, the intracellular mechanisms after the increase in [Ca2+]i are probably common to the vasocontractile responses mediated by alpha 1- and alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1990

The changes of antioxidative enzyme activities in equine erythrocytes following exercise.

The change in activities of 3 major antioxidative enzymes in equine erythrocytes, superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and catalase, was investigated in order to evaluate the effect of exercise. Blood samples were obtained from 11 thoroughbred horses before and immediately after vigorous exercise which induced the increase of plasma lipid peroxide (Lpx) concentration from 1.16 +/- 0.40 nmol/ml to 1.29 +/- 0.34 nmol/ml. Following the exercise, the GSHpx activity in erythrocytes was significantly reduced from 69 +/- 10 IU/gHb to 65 +/- 8 IU/gHb, whereas SOD and catalase activities were not changed. Effects of an antioxidative compound, containing selenium and vitamin E(Se-E), on the response of antioxidative enzyme activities following the exercise were examined. Seven horses were injected intramuscularly with Se-E(Se:25 mg, vitamin E:54.8 mg) and received the same vigorous exercise. After Se-E treatment, plasma Lpx levels before the exercise were decreased from 1.24 +/- 0.09 nmol/ml to 0.86 +/- 0.03 nmol/ml, however, SOD, GSHpx, and catalase activities were not varied. The Se-E treatment slightly prevented the decrease in GSHpx activity and the increase in plasma Lpx level after the exercise, having no effect on SOD and catalase activities. These results suggested that the changes of GSHpx activity in erythrocytes might reflect the protective condition against exercise-induced lipid peroxidation.

Animals↗
PubMed1990

Comparison of various motion stimuli on motion sickness and acquisition of adaptation in Suncus Murinus.

Effects of various types of motion stimuli were compared to investigate optimum method to elicit motion sickness and adaptation in Suncus murinus (suncus). Three different direction of shaking in the horizontal plane, back and forth, right and left and revolving, induced emetic response to the similar extent. However, vertical shaking was far less effective in inducing motion sickness. Mild and severe horizontal shaking (15 min per day) was continued for 14 days and emetic response to standard motion stimulus was compared before and after the training. The severe daily acceleration strongly depressed the susceptibility to motion stimulus. The mild acceleration which was not emetic stimulus in itself also remarkably attenuated the vomiting response to standard motion stimulus. These results indicate that 1) the emetic responsiveness of the suncus does not depend on the modes of shaking as long as the direction is in the horizontal plane, 2) the suncus is relatively refractory to the vertical linear acceleration and 3) the adaptation to motion stimulus does not develop on the latest peripheral steps of the vomiting reflex pathways.

Adaptation, Physiological↗