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N Matsuki

Publications and source records attributed to N Matsuki.

At least 91 records · Page 5Linked to original sources
PubMed1996

The pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus.

This paper is the first to describe aspects of the mechanics of retching in the insectivore Suncus murinus (house musk shrew) and in an animal of such a small size (approximately 50 g). In anaesthetised animals using the novel stimulus of mechanical stimulation of the upper gastrointestinal tract as the provocative stimulus the frequency of retching was found to be about 4 retches/s, a much higher frequency than in other species (dog, cat, ferret). These studies show that quantification of retching in Suncus cannot be undertaken using direct observation. The temporal pattern of the emetic response was characterised in conscious Suncus using motion (1 Hz, 5 min) and nicotine (20 mg/kg s.c.). The ultrapotent capsaicin analogue resiniferatoxin (100 micrograms/kg s.c.) was discovered to be highly emetic and comparative studies showed that nicotine and resiniferatoxin induced the most intense responses with episodes (retches and a vomit) occurring every 10-15 s. The retching response to mechanical stimulation in the anaesthetised Suncus was not blocked by a 5-HT3 receptor antagonist (granisetron, 1-5 mg/kg s.c.), a tachykinin NK1 receptor antagonist (CP-99,994 20 mg/kg s.c. dihydrochloride salt (9+) -(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) or morphine (2 mg/kg s.c.) but was blocked by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT 100 micrograms/kg s.c.). Suncus appears to be a suitable animal in which to study the pharmacology of the emetic response to mechanical stimulation of the gut. The results are discussed in the light of studies of the pharmacology of emesis in other species.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Basic fibroblast growth factor modulates synaptic transmission in cultured rat hippocampal neurons.

Basic fibroblast growth factor (bFGF) is one of the effective growth factors that protect neurons against excitotoxic/ischemic injury and promote neuronal survival. In the present study, we examined the acute modulative effect of bFGF on synaptic transmission by monitoring spontaneous intracellular Ca2+ ([Ca2+]i) oscillation, the amplitudes of which reflect excitatory and inhibitory inputs. The hippocampal cells from embryonic day 18 rats were cultured for 11-14 days, and changes in [Ca2+]i of single neurons were measured by a microfluometrical technique with fura-2. The amplitude of spontaneous oscillation was decreased by 10 ng/ml bFGF, but not by nerve growth factor (10-1000 ng/ml). Acidic FGF (1000 ng/ml) had a weaker depressant effect. The effect of bFGF was counteracted by suramin. bFGF did not affect the increase in [Ca2+]i evoked by glutamate agonists, NMDA or kainate, indicating that glutamate receptors are not involved in the mechanism. This is supported by similar results that kainate-evoked current was not affected by bFGF. On the other hand, bicuculline masked the effect of bFGF on the Ca2+ oscillation. But GABA-evoked current was slightly decreased by bFGF. These results suggest the possible role of bFGF in modulating GABAergic rather than glutamatergic neurotransmission.

Animals↗
PubMed1996

A promiscuous T cell hybridoma restricted to various I-A molecules.

In a previous study, we identified T cell receptor and major histocompatibility complex (MHC) contact sites on the pigeon cytochrome c p43-58 peptide. Positions 46 and 54 of p43-58 were shown to be the MHC-binding sites. Specific amino acids were identified on the MHC-binding sites which bound to the relevant I-A molecule. In the present study, using NOD (I-Ag7) mice, we established a T cell hybridoma specific for a p43-58 analog 46R50E54A with arginine (R) and alanine (A) at positions 46 and 54, respectively. Interestingly, NOE 33-1-2 recognized 46R50E54A in the presence of not only I-Ag7, but also I-Ad, s, u and v. In contrast to previous reports that promiscuous T cells were able to recognize peptide antigens with various HLA-DR or I-E molecules consist of monomorphic alpha and polymorphic beta chains, the promiscuous T cell clone NOE33-1-2 recognized peptides with various I-A molecules lacking the monomorphic chain.

Amino Acid Sequence↗
PubMed1996

Regional difference in sympathetic neurotransmitter- and Ca2+ channel-mediated responses in rat vas deferens.

1. Pharmacological properties were compared in the epididymal and prostatic portions of the rat vas deferens. 2. Contractile response to norepinephrine (NE) was larger in the epididymal portion, in spite of the smaller diameter in this region. In contrast, contraction evoked by ATP or alpha,beta-methylene ATP (alpha,beta-mATP) was larger in the prostatic portion. The sensitivities to NE but not to alpha,beta-mATP are different in these portions. 3. ATP or NE facilitated the contraction induced by the other agonist, suggesting that they cooperatively elicit smooth muscle contraction. This cooperation was observed in both portions. 4. Neither the contraction elicited by the addition of Ca2+ to smooth muscle depolarized with 63.7 mM extracellular K+ nor the relaxation by nifedipine of the depolarized smooth muscle precontracted with 1.8 mM extracellular Ca2+ was regionally different. However, Bay k 8644 elicited contraction only in the epididymal portion. A combination of 5 mMK+ with Bay k 8644 also caused oscillatory contraction in the prostatic portion. 5. A radioligand binding study was performed using the microsomal fraction prepared separately from these portions. Both the dissociation constant and the maximum binding for 3H-nimodipine were smaller in the epididymal fraction than in the prostatic fraction. 6. These results suggest that 1. the NE-elicited contraction is more pronounced in the epididymal portion, 2. the purinoceptor-mediated contractions along the vas deferens are less heterogeneous, and 3. although the sensitivity to Bay k 8644 is higher in the epididymal portion, Ca2+ channel-mediated responses are not regionally different when they are fully activated.

Adenosine Triphosphate↗
PubMed1996

Effects of coculture with the septum on the expression of long-term potentiation in organotypic hippocampal slice cultures.

The hippocampus receives major afferent innervation from the septum. Using organotypic slice culture, we investigated whether coculture with the septum would modulate transmission and plasticity of hippocampal synapses. In septo-hippocampal cocultures, acetylcholinesterase-positive fibers extending from septal tissue to hippocampal slice were observed. Septo-hippocampal cocultures exhibited larger magnitude of long-term potentiation (LTP) in CA3 and CA1 synapses than hippocampal slices cultured alone, without significant changes in maximal synaptic responses and macroscopic hippocampal cytoarchitecture. Unexpectedly, the facilitatory effect on hippocampal LTP was independent of afferent innervation from the septum, because (1) electrical stimulation of the cocultured septum suppressed the induction of hippocampal LTP, (2) chronic application of 1 microM atropine did not block the facilitatory effect, and (3) septo-hippocampal cocultures without contact with each other still showed a larger magnitude of LTP than hippocampal slices alone. These results suggest that diffusible factor(s) released from the septal tissue modulate functional maturation of hippocampal synapses as to the ability to support synaptic plasticity.

Animals↗
PubMed1996

Improvement of fatigue and acceleration of recovery from stress-induced deficient sexual behavior in mice following oral administration of soft-shelled turtle powder.

Effects of oral administration of cryomilled powder of the soft-shelled turtle (SST powder) on forced-exercise performance and stress-induced reduction in sexual and learning behavior were studied in mice. In the fatigue-preventive experiment, the SSt powder was administered orally to mice which were forced to climb a descending rope for 60 min a day. The treatment significantly improved the daily performance of the mice. In the stress recovery experiment, male mice were hanged from the tail and forced to swim using their fore paws for 30 to 60 min everyday. Stress significantly reduced sexual behavior and memory retrieval (step down test). Daily oral administration of the SST powder significantly attenuated this decline in sexual behavior. However, the effects on memory retrieval were not statistically significant. These results suggest that administration of SST powder attenuates fatigue and accelerates recovery from stress in mice.

Administration, Oral↗
PubMed1996

Anti-tumor effects of orally administered soft-shelled turtle powder in mice.

The effects of oral administration of cryomilled powder of the soft-shelled turtle (SST powder) on solid and ascites tumor-bearing C3H/He mice were studied. The SST powder was administered orally at a dose of 100 or 500 mg/kg/d for two or four weeks, and then MH134 hepatoma cells were inoculated; oral administration was continued after inoculation. Treatment with the SST powder attenuated the increase in diameter and weight of the tumor and prolonged the survival of mice with solid tumors. However, the same treatment did not show any significant effect in mice with ascites tumor, indicating that the SST powder has no direct killing action on tumor cells. These results suggest that oral administration of the SST powder decreases the growth of solid tumors possibly by activating the host immune system.

Administration, Oral↗
PubMed1996

[Mechanisms of cytotoxic drug-induced emesis and its prevention].

In this review, I have attempted to provide an overview of the pathways by which cytotoxic drugs induce emesis. The mechanisms of serotonin 5-HT3 antagonists and new antiemetics are also discussed. Old data especially from the experiments employing area postrema ablation must be re-evaluated because it is likely that the operation has damaged other important nucleus in the brain stem. Therefore, the concept of the chemoreceptor trigger zone and "vomiting center" proposed by Borison et al. in 1950s is questionable. Nausea and vomiting caused by cytotoxic drugs have been a serious problem in anti-cancer therapy and prompted lots of scientists to find the mechanism and to develop antiemetics. Effectiveness of 5-HT3 antagonists were shown in late 1980s, and now they are clinically available. I have investigated their mechanisms using Suncus murinus and proposed that the pathways by which cisplatin, one of most emetogenic drugs, induces emesis are as follows: 1) cisplatin is converted to an active metabolite(s), 2) the metabolite(s) somehow produces oxygen free radicals in the enterochromaffin cells, 3) the free radicals release serotonin, 4) the released serotonin stimulates 5-HT3 receptors located on the vagus afferents, 5) impulses are transmitted to the brain stem, or emetic pattern generator and initiate emetic reflex. Therefore, scavengers of free radicals and antioxidants can be a new type of antiemetic drug.

Animals↗
PubMed1996

Intracellular calcium oscillation in cultured rat hippocampal neurons: a model for glutamatergic neurotransmission.

Neurons can form a synaptic network in culture and show spontaneous oscillation of intracellular Ca2+ concentration ([Ca2+]i). In the present study, spontaneous oscillation of [Ca2+]i was characterized in cultured hippocampal neurons. The oscillation was blocked completely by tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and nicardipine, while DL-2-amino-5-phosphonovaleric acid (APV) showed only a partial depression of the increase in [Ca2+]i. These results suggest that the oscillation in [Ca2+]i is mainly mediated by non-N-methyl-D-aspartate (NMDA) type glutamatergic transmission. The oscillation of [Ca2+]i may be a good model for analyzing glutamatergic transmission and synapse formation.

2-Amino-5-phosphonovalerate↗
PubMed1996

Nitric oxide but not carbon monoxide is involved in spatial learning of mice.

The aim of the present study was to elucidate the role of carbon monoxide (CO) in learning and to compare it with that of nitric oxide (NO). Effects of an inhibitor of heme oxygenase which produces CO, Zn-protoporphyrin IX, on passive avoidance learning and spatial learning in mice were examined using step through, step down and water maze tests. Zn-protoporphyrin IX (10, 20 nmol, i.c.v.) affected neither type of learning. In contrast, N-omega-nitro-L-arginine (40 nmol, i.c.v.), an inhibitor of NO synthase, impaired spatial learning, but not passive avoidance learning. These results suggest that NO but not CO is involved in spatial learning.

Animals↗
PubMed1996

Effects of depletion of T cell subpopulations on the course of infection and anti-parasite delayed type hypersensitivity response in mice infected with Babesia microti and Babesia rodhaini.

To elucidate the role of T cell subpopulations in the protective cell-mediated immune response at the initial phase of infection with Babesia microti (BM) and B. rodhaini (BR), the changes in the course of infection and anti-parasite delayed type hypersensitivity (DTH) response after BM or BR inoculation were investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+ T cells strongly enhanced the resistance to BM infection, whereas it increased the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. The anti-parasite DTH response in BM-infected mice was significantly enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH response was observed in BR-infected mice. From these results, it was suggested that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM- and BR-infected mice, resulting in the difference in their course of infection.

Animals↗
PubMed1995

Defect in assembly process of very-low-density lipoprotein in suncus liver: an animal model of fatty liver.

We previously showed that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) was very low. There are three possible explanations for the low level of apo B in the animals: low synthetic rate, low secretion rate, and rapid catabolism in the circulation of apo B. We measured post-heparin lipolytic activity (lipoprotein lipase activity), which plays a key role in the catabolism of apo B-containing lipoprotein, VLDL, and found no difference between rats and suncus. We also investigated the hepatic synthetic rate of apo B by liver perfusion studies. Newly synthesized apo B in the suncus liver was detected by immunoprecipitation and found to amount to 12.5% of that in rats. The secretion rate of VLDL in suncus, which was estimated by intravenous injection of Triton WR1339, was 13.8% of that in rats. These two results suggest that there is no major defect in the secretory process. We separated Golgi apparatus from rat and suncus livers, and found much fewer lipoprotein particles in suncus than in rat Golgi apparatus. This evidence suggests that there is no defect in the lipolytic process or hepatic secretory process of apo B-containing lipoprotein, VLDL, but there may be a defect in the assembly process of VLDL and/or in the synthetic process of apo B in suncus. Such a defect may be one of the reasons for starvation-induced fatty liver in suncus.

Animals↗
PubMed1995

Role of acyl coenzyme A cholesterol acyltransferase in intrahepatic processing of apo B-lipoprotein in suncus.

We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apoB) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprotein, VLDL) may be one of the reasons for the low level of plasma apo B and for induction of fatty liver by starvation in suncus. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is very low in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembling process of VLDL. In this study, we investigated the effect of cholesterol-feeding, which induces an increase in triglyceride and cholesteryl ester of the liver as a consequence of the induction of both intestinal and hepatic ACAT activities, on the secretion of VLDL. Although the basal ACAT activity of intestinal mucosa was high, cholesterol-feeding did not induce either an increase in plasma lipid or an increase in intestinal ACAT activities in suncus. The hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339, which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused a slight increase in hepatic triglyceride and cholesteryl ester but no increase either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Blockade of motion- and cisplatin-induced emesis by a 5-HT2 receptor agonist in Suncus murinus.

1. The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOl), a 5-hydroxytryptamine 5-HT2A/5-HT2C receptor agonist, on motion- and cisplatin-induced emesis were studied in Suncus murinus. Subcutaneous injection of DOl, 30 min prior to the emetic stimuli, dose-dependently blocked the emesis induced by motion sickness and cisplatin (20 mg kg-1, i.p.) with estimated ID50 values of 640 and 780 micrograms kg-1, respectively. 2. alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT), a peripheral 5-HT2A/5-HT2C receptor agonist, had no effect on motion- and cisplatin-induced emesis. 3. The antiemetic effects of DOl on motion- and cisplatin-induced emesis were attenuated by preadministration of ketanserin, a selective 5-HT2A receptor antagonist. 4. The present results suggest an inhibitory role for central 5-HT2 receptors in the emetic reflex mechanism and that a 5-HT2 receptor agonist may be a useful tool to investigate the involvement of 5-HT receptors in the emetic reflex.

Amphetamines↗
PubMed1995

Effects of aminoglycoside antibiotics on cholinergic autonomic nervous transmission.

The effects of eight aminoglycoside antibiotics, gentamicin, neomycin B, ribostamycin, dibekacin B, kanamycin A, streptomycin, tobramycin and amikacin, and two non-aminoglycoside antibiotics, tetracycline and ampicillin, on cholinergic autonomic nervous transmission were studied using isolated guinea-pig ileum preparation. The aminoglycoside antibiotics blocked the transmurally elicited twitches of the ileum in a concentration-dependent manner. The blocking effect of aminoglycosides was biphasic, i.e., an initial reduction followed by a spontaneous partial recovery. Dibekacin was the most potent parasympathetic inhibitor, followed by neomycin B, tetracycline, gentamicin, streptomycin, kanamycin A, tobramycin, ribostamycin, and amikacin. Ampicillin had no blocking effect. The tested antibiotics did not affect acetylcholine (ACh)-induced contraction of the ileum, except for high concentrations of neomycin B, gentamicin, and streptomycin. The three antibiotics shifted the dose-response curves for ACh to the right without affecting the maximal contraction. Naloxon, yohimbine, hexamethonium and choline chloride failed to eliminate the blocking effect of the antibiotics on twitches of the ileum induced by transmural stimulation. However, increase of the extracellular Ca ion concentration virtually abolished the blockade. Dibekacin blocked the evoked but not the spontaneous release of ACh and shifted the dose-response curve of CaCl2-dependent transmurally elicited contractions of the ileum to the right. These results suggest that the site for the block of aminoglycosides is mainly the cholinergic nerve terminal, where they reduce the available Ca ions required for the release of ACh.

Acetylcholine↗
PubMed1994

5-HT1A receptor-mediated inhibition of N-type calcium current in acutely isolated ventromedial hypothalamic neuronal cells.

The effects of serotonin (5-hydroxytryptamine: 5-HT) and 5-HT1A agonist on voltage-gated calcium channels (VGCCs) in acutely isolated ventromedial hypothalamic (VMH) neuronal cells were studied using whole-cell configuration of the patch-clamp technique. 5-HT at 10 microM inhibited inward calcium current reversibly in 80% of cells. This inhibition was specific to N-type current. Because pindolol blocked the effect of 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) mimicked the effect of 5-HT, the inhibitory effect of 5-HT appeared to be mediated via the 5-HT1A receptor. In the fura-2 fluorometry method, 8-OH-DPAT attenuated the [Ca2+]i increase induced by the depolarization stimulus of 50 mM K+. These results indicate that 5-HT suppresses Ca2+ entry through N-type channels in the VMH neurons via the 5-HT1A receptor and that the stimulating effect of 8-OH-DPAT on feeding behavior may be mediated by the blocking of Ca2+ entry through N-type channels.

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