Biomedical subjects

N Matsuki

Publications and source records attributed to N Matsuki.

At least 109 records · Page 6Linked to original sources

PubMed1994

Effect of starving and refeeding on lipid metabolism in suncus.

We have previously reported that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food, and that apolipoprotein B (apo B) is not actively synthesized in the liver. In the present paper we describe the effect of starving and refeeding on lipid and lipoprotein metabolism in suncus, in order to explore the mechanisms of induction of fatty liver by starving and of its improvement by refeeding. Starvation induced increase in triglyceride content and decrease in glycogen content of the liver. Although the glycogen content returned to the level before starvation at 12 h after refeeding, the triglyceride content decreased gradually but did not reach the prestarvation level even at 24 h after refeeding in suncus. Plasma lipids, glucose, and insulin levels were decreased by starvation and returned to the levels before starvation between 8 and 24 h after refeeding. On the other hand, the plasma levels of free fatty acid and ketone bodies were elevated significantly by starvation and decreased rapidly by refeeding. These responses to starvation and refeeding, except for the change in hepatic triglyceride, are in common with other experimental animals, suggesting that there are no abnormalities in glucose metabolism or in fatty acid metabolism in suncus. In conclusion, the fatty liver induced by starvation in suncus may be caused by impaired triglyceride transport out of the liver, for which apolipoprotein B is mostly responsible, as reported previously.

Animals↗

PubMed1994

Deficiency of acyl CoA cholesterol acyl transferase activity in suncus liver.

We reported previously that apolipoprotein B is not actively secreted from suncus liver. In the present study we have investigated the hepatic cholesterol metabolism, which plays a critical role in the secretion of apo B. We found that the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in suncus liver is high and that acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity is almost absent in contrast to rats. As a result, the hepatic content of cholesterol ester, upon which apoprotein B secretion partly depends, is very low in suncus. The deficiency of ACAT activity may cause the defect in active secretion of apoprotein B-containing lipoproteins in suncus.

Animals↗

PubMed1994

Induction of emesis in Suncus murinus by pyrogallol, a generator of free radicals.

1. We investigated whether or not pyrogallol, a generator of free radicals, is emetogenic in Suncus murinus, the house musk shrew. Pyrogallol (i.p.) caused dose-dependent emesis in suncus with an ED50 value of 77.3 mg kg-1. At a dose of 128 mg kg-1, all suncus vomited with mean latency of 18.8 +/- 5.2 min and the number of vomiting episodes was 8.6 +/- 2.9. 2. The prophylactic effects of N-(2-mercaptopropionyl)-glycine (MPG), an antioxidant, and tropisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were studied. Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively. 3. Pyrogallol-induced emesis was completely prevented by surgical abdominal vagotomy. 4. The present results indicate that pyrogallol-induced emesis is characteristically very similar to that caused by cisplatin and support the idea that generation of free radicals causes the release of peripheral 5-HT, which stimulates vagal afferent sensory nerves to cause emesis.

Animals↗

PubMed1994

Role of cholinergic neurotransmission in the amygdala on performances of passive avoidance learning in mice.

To clarify the role of cholinergic neurons in the amygdala on learning and memory, scopolamine was injected topically into the bilateral amygdala of mice, and the ability to perform two types of passive avoidance tasks (step-through and step-down) was investigated. On the first day mice performed the learning trial and on the second day their retention was tested. Scopolamine (0.5 or 1 microgram/site) was injected bilaterally into the amygdala 30 min before or immediately after the learning trial or 30 min before the testing trial. Scopolamine impaired the performance ability of the mice dose-dependently only when it was injected 30 min before the learning trial. The results coincided well with the effect of scopolamine injected intraperitoneally. Taken together, these results suggest that the site of action for scopolamine to cause anterograde amnesia is the amygdala, and that cholinergic neurons projecting to the amygdala play an important role in memory acquisition in the two passive avoidance tasks.

Amygdala↗

PubMed1994

Antiemetic effects of serotonergic 5-HT1A-receptor agonists in Suncus murinus.

The antiemetic effects of six serotonergic 5-HT1A-receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetrarin (8-OH-DPAT), 4-(4-[4-(2-pyrimidinyl)piperazin-1-yl]butyl)-2,3,4,5- tetrahydro-1,4-benzoxazepine-3,5-dione (SUN8399), buspirone, gepirone, ipsapirone and tandospirone, against motion sickness were investigated in Suncus murinus. Subcutaneous injection of all six agonists completely and dose-dependently suppressed motion-induced emesis. Pretreatment with 8-OH-DPAT or SUN8399 dose-dependently inhibited emesis elicited by nicotine (4.0 mg/kg, s.c.), veratrine (0.7 mg/kg, s.c.), cisplatin (20 mg/kg, i.p.) and copper sulfate (40 mg/kg, p.o.). These results suggest that serotonergic 5-HT1A-receptor agonists are effective as anti-motion sickness drugs, and these drugs may block a common mechanism(s) for the emetic reflex of the suncus because the antiemetic effects of the 5-HT1A-receptor agonists were exerted irrespective of the stimulus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Involvement of carbon monoxide in long-term potentiation in the dentate gyrus of anesthetized rats.

To elucidate the role of carbon monoxide (CO) in hippocampal long-term potentiation (LTP), the effect of an inhibitor of heme oxygenase, which produces carbon monoxide, was investigated in the dentate gyrus of anesthetized rats. Administration of zinc protoporphyrin IX (100 nmol, i.c.v.) 30 min before the tetanic stimulation of 30 pulses at 60 Hz attenuated the intensity of LTP. However, this drug did not affect the established LTP. These results suggest that CO participates in the generation of LTP in vivo.

Action Potentials↗

PubMed1994

[A case of cutaneous and brain metastasis of gastric carcinoma, treated effectively by chemotherapy with CDDP, MMC, etoposide and 5'-DFUR].

A case of cutaneous and brain metastasis of gastric carcinoma, treated effectively by chemotherapy, is reported. The patient was a 67-year-old female. She underwent total gastrectomy for advanced gastric carcinoma with direct invasion to liver. Six months later, she was admitted with headache and multiple skin nodules on the trunk. CT showed two round tumor shadows on the left side of brain, and a skin biopsy specimen revealed poorly differentiated adenocarcinoma. Chemotherapy with 10mg of CDDP, 2mg of MMC, 150mg of etoposide and 300mg/day of 5'-DFUR was performed. After the third course of chemotherapy, cutaneous and brain metastasis disappeared. Although the patient died of pulmonary metastasis 24 weeks after, cutaneous and brain metastasis disappeared 12 weeks.

Adenocarcinoma↗

PubMed1993

Endogenous nitric oxide inhibits NMDA- and kainate- responses by a negative feedback system in rat hippocampal neurons.

Involvement of endogenous nitric oxide (NO) on glutamate receptor-mediated response was investigated in neuronal cells cultured from embryonic rat hippocampus. L-NG-Nitroarginine (NOARG), a NO synthase inhibitor, augmented NMDA- and kainate-induced increase in intracellular Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorometry. However, quisqualate-induced response was not affected. The potentiating effect of NOARG was blocked by L-arginine, a substrate for NO synthase. NOARG was also effective when added after glutamate-induced response had reached a steady-state. Hemoglobin itself increased the basal level of [Ca2+]i at concentrations higher than 10 mM, and treatment of the cells with 1.0 mM hemoglobin had no effect on NMDA response. 8-Bromo-cyclic GMP was not effective on NMDA response. These results suggest that endogenous NO inhibits NMDA- and kainate-induced increase in [Ca2+]i as a negative feedback system independent of guanylate cyclase activation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

Effects of iron and deferoxamine on cisplatin-induced emesis: further evidence for the role of free radicals.

The effects of ferric chloride and deferoxamine, an iron chelator, on cisplatin-induced emesis were studied in Suncus murinus. Pretreatment with ferric chloride (FeCl3, 16-64 mg/kg) increased the number of 20 mg/kg cisplatin-induced vomiting episodes. Deferoxamine (256 mg/kg) significantly reduced the number of vomiting episodes and prolonged the latency. These results further support the involvement of free radicals in the generation of cisplatin-induced emesis.

Animals↗

PubMed1993

Involvement of free radicals in cisplatin-induced emesis in Suncus murinus.

The participation of free radicals in cisplatin-induced emesis was investigated in the house musk shrew, Suncus murinus. Thiobarbituric acid (TBA) values, which indicate the degree of lipid peroxidation, in brain, liver and small intestine were increased significantly 60 min after the treatment with cisplatin (20 mg/kg, i.p.). Moreover, cisplatin (20 mg/kg, i.p.)-induced emesis was prevented by intraperitoneal injection of N-(2-mercaptopropionyl)glycine (MPG), a radical scavenging agent, with ID50 value of 130 mg/kg. However, MPG did not block the emesis induced by copper sulfate (40 mg/kg, p.o.), veratrine (0.5 mg/kg, s.c.) or serotonin (10 mg/kg, i.p.). We also investigated the effects of superoxide dismutase conjugated to polyethylene glycol and catalase, but the number of vomiting episodes and latency did not change significantly when these agents were intraperitoneally injected 30 min prior to or 20 min after the administration of cisplatin. MPG did not affect the antitumor effect of cisplatin tested in vitro. These results suggest that free radicals mediate emesis caused by cisplatin and that radical scavengers may become a new class of prophylactic drug against cancer-chemotherapeutic drug-induced emesis.

Animals↗

PubMed1993

Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain.

The effects of electroconvulsive seizure and anti-convulsant drugs on induction of mRNA of heat shock protein were studied in mouse brain. Electrical shock induced mRNA of heat shock cognate protein (HSC70), but not heat shock protein (HSP70) mRNA. The induction was maximum 1 h after the ECS and continued for several hours, followed by long-lasting depression. Diazepam slightly prevented the ECS, but strongly attenuated the induction of HSC70 mRNA. Whereas phenytoin, which blocked the seizure, did not decrease but delayed the induction of HSC70 mRNA. The present results suggest that HSC70 mRNA level is increased with the ECS and that the induction level did not necessarily correlate the severity of the seizure.

Animals↗

PubMed1993

Effect of fibroblast growth factors on calcium currents in acutely isolated neuronal cells from rat ventromedial hypothalamus.

Three types of voltage-gated calcium currents (VGCCs) were recorded using the whole-cell configuration of the patch-clamp technique in acutely isolated neurons from rat ventromedial hypothalamus. They consist of a transient low-threshold current, a nicardipine-sensitive L-type current and an omega-CgTX sensitive N-type current. Basic fibroblast growth factor (bFGF) at a concentration of 10-100 ng/ml augmented the L-type current immediately after the addition to the bath. However, the effect was observed only in 29% of the cells tested. Acidic fibroblast growth factor did not affect the VGCCs in the cells. It is suggested that part of the neurotrophic effects of bFGF are attributable to the increase in the L-type calcium current.

Animals↗

PubMed1993

Characterization of serum lipoproteins from Suncus: a candidate animal model for abetalipoproteinemia.

We have previously reported that fatty liver was induced in a novel experimental animal, Suncus murinus (suncus), by 24-h fasting and that apolipoprotein B (apo B) was not actively synthesized in the liver. However, a faint signal of apo B mRNA was detected in the liver, suggesting possible synthesis of apo B. Small amounts of VLDL and LDL have been separated from suncus serum by ultracentrifugation. Electron microscopic study of the lipoproteins revealed the existence of small particles in VLDL. High performance liquid chromatographic analysis of the lipoproteins showed that the peaks of TG and cholesterol were mainly at the HDL fraction. These results indicate the existence of lipoproteins as small as HDL which were rich in TG and floated at the density of VLDL upon ultracentrifugation. Apolipoprotein analysis showed two bands of 500- and 200-kDa proteins in VLDL and LDL. Western blot analysis using antibody against the 500-kDa protein revealed reaction not only with suncus 500- and 200-kDa proteins but also with human apo B-100. In conclusion, a small amount of apo B is transported in the suncus serum as VLDL and LDL, although almost all lipid is packed in HDL-size particles.

Abetalipoproteinemia↗

PubMed1993

Blockade by calmodulin inhibitors of Ca2+ channels in smooth muscle from rat vas deferens.

1. Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W-7 and calmidazolium) on Ca2+ channels were investigated in smooth muscle from rat vas deferens. 2. All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7 mM). The order of potency for the relaxation was trifluoperazine > W-7 > calmidazolium. 3. In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [3H]-nimodipine binding. Trifluoperazine and W-7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation. 4. Ba2+ current flowing through voltage-gated Ca2+ channels was measured under whole-cell voltage-clamp conditions in isolated smooth muscle cells. The Ba2+ current was suppressed by the three calmodulin inhibitors in the concentration-range where inhibition of [3H]-nimodipine binding was observed. Neither voltage-dependence nor the inactivation time course of Ba2+ current were affected by these compounds. 5. The results suggest that the calmodulin inhibitors directly block Ca2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W-7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds.

Animals↗

PubMed1993

Inhibitory effect of aniracetam on N-type calcium current in acutely isolated rat neuronal cells.

Effects of aniracetam on whole-cell calcium currents were studied in acutely isolated neuronal cells from postnatal rat ventromedial hypothalamus. There were three types of inward calcium currents, one low-threshold transient current and two high-threshold sustained currents. The nicardipine sensitive L-type current was activated at -20 mV or more depolarized potentials, and the omega-conotoxin sensitive N-type current was recorded at more positive potentials than the L-type. Aniracetam inhibited the N-type current in a dose-dependent manner without affecting the other two types of calcium currents. The effect appeared soon after the addition and lasted for several minutes during washing. Since the N-type current is thought to regulate the release of transmitters, the inhibitory effect may contribute to the nootropic property of aniracetam by modifying the neurotransmission.

Animals↗

PubMed1993

Pharmacological properties of blood pressure and heart rate control in suncus.

Blood pressure and heart rate and responses to various physiological substances in suncus were characterized and compared with those in mice. The blood pressures of the two species were similar, but the heart rate of suncus (about 400 beat/min) was significantly lower than that of mice. Norepinephrine increased the blood pressure but decreased the heart rate in suncus. The latter was blocked by cervical vagotomy. Sensitivities to acetylcholine and isoproterenol were lower in suncus. These results suggest that regulation of blood pressure and heart rate in suncus is very unique and different from the well-defined system of the rodents.

Acetylcholine↗

PubMed1993

Adenosine induces contractions in suncus ileum.

Purinoceptor-mediated responses were characterized in the ileum of Suncus murinus. Adenosine as well as adenosine 5'-triphosphate (ATP) contracted the ileum in a concentration-dependent manner. Contractile responses to transmural electrical stimulation were attenuated by adenosine only at high concentrations. Theophylline competitively blocked the adenosine-induced contraction. Atropine also inhibited the adenosine-induced contraction but in a non-competitive manner. The ATP-induced contraction was not affected by theophylline, atropine or alpha, beta-methylene ATP. Indomethacin shifted the concentration-response curves for adenosine and ATP to the right. These results suggest that adenosine elicited contractions via direct stimulation of postsynaptic P1-purinoceptors and postsynaptic potentiation of the acetylcholine response. Suncus ileum will be a unique model for the analyses of purinoceptor-mediated responses.

Adenosine↗

PubMed1993

X-irradiation-induced emesis in Suncus murinus.

X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0 +/- 2.4 times with a latency of 20.0 +/- 2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X-irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT3 receptor antagonist) with an ID50 value of 29 micrograms/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X-irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents.

Animals↗