Search PubMed⌕ Search

Biomedical subjects

K Murase

Publications and source records attributed to K Murase.

At least 145 records · Page 8Linked to original sources
PubMed1996

Insulin increases distinct species of 1,2-diacylglycerol in isolated perfused rat heart.

Insulin and glucose increase the synthesis of 1,2-diacylglycerol (1,2-DAG), the physiological activator of protein kinase C (PKC) in a variety of tissues and cells. The effects of insulin and glucose on the abundance and fatty acid composition of 1,2-DAG were investigated in isolated perfused rat hearts with the use of capillary gas chromatography and 1,2-dipentadecanoin as an internal standard. A high concentration of insulin (25 mU/ mL) significantly increased cardiac contractility and reduced coronary flow. In addition, perfusion with 25 mU/mL insulin induced significant increases of 18.2% and 26.4% in 1,2-DAG mass after 5 and 30 minutes, respectively, in the presence of 8.6 mmol/L glucose, whereas there was no increase in 1,2-DAG with 2.5 mU/mL insulin. Analysis of the fatty acid composition of 1,2-DAG showed that only species containing specific fatty acids (16:0, 18:1, and 18:2) were increased in response to insulin. In contrast, an increase in glucose concentration in the perfusion medium from 3 to 17 mmol/L had no effect on the total mass or fatty acid composition of 1,2-DAG, cardiac contractility, or coronary flow. Addition of a high insulin concentration to the high-glucose medium increased the abundance of 1,2-DAG containing 16:0, 18:1, and 18:2 fatty acids, as well as cardiac contractility. It is concluded that the effect of insulin on cardiac contractility may be related to the associated increase in 1,2-DAG abundance.

Animals↗
PubMed1996

Impairment of antioxidants in colonic epithelial cells isolated from trinitrobenzene sulphonic acid-induced colitis rats. Protective effect of rebamipide.

BACKGROUND: The functional status of glutathione, its related enzymes, and Cu,Zn-superoxide dismutase in colonocytes isolated from rats with trinitrobenzene sulphonic acid-induced colitis, and the effect of rebamipide (a scavenger) on these antioxidants and on colitis, were studied. METHODS: The rats were treated with rebamipide, killed on day 14, and compared with controls. Glutathione and enzymatic activities were spectrophotometrically estimated. The effect of rebamipide on colitis was also assessed histologically and by myeloperoxidase activity. RESULTS: In controls the concentration of glutathione and the activities of glutathione S-transferase and Cu,Zn-superoxide dismutase were decreased, but that of glutathione peroxidase was increased. Rebamipide prevented the impairment of these enzymes, restored the concentration of glutathione, and attenuated (low damage scores and myeloperoxidase activity) the severity of the colitis. CONCLUSIONS: These features suggest that the impairment of antioxidants is closely related to the development of the inflammatory lesions, and rebamipide has a beneficial effect on experimental colitis.

Alanine↗
PubMed1996

YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist.

We investigated the pharmacological properties and neuroprotective actions of a novel alpha-amino-3-hydroxy-5-methylisoxazole-y-propionate (AMPA)/kainate receptor antagonist, [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride (YM90K); formerly YM900], in comparison with those of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX). YM90K selectively displaced [3H]-AMPA binding (Ki = 0.084 microM) and was less potent in inhibiting [3H]-kainate (Ki = 2.2 microM), [3H]-L-glutamate (N-methyl-D-aspartate-sensitive site; Ki > 100 microM) and [3H]-glycine (strychnine-insensitive site; Ki = 37 microM) binding to rat brain membranes. YM90K co-injected with AMPA or kainate into the rat striatum protected cholinergic neurons against AMPA- or kainate-induced neurotoxicity. YM90K showed potent suppressive activity against audiogenic seizure in DBA/2 mice; ED50 values of YM90K and NBQX against tonic seizure were 2.54 and 7.17 mg/kg (i.p.), respectively. The duration of the anticonvulsant effects of YM90K and NBQX was 30 min, indicating that both compounds possess short action. In a global ischemia model, YM90K (15 mg/kg i.p. x 3), NBQX (30 mg/kg i.p. x 3) and CNQX (60 mg/kg i.p. x 3) significantly prevented the delayed neuronal death in the hippocampal CA1 region in Mongolian gerbils when administered 1 h after 5-min ischemia. In addition, the therapeutic time window for the neuroprotective effect of YM90K (30 mg/kg i.p. x 3) was 6 h. In a focal ischemia model, YM90K (30 mg/kg i.v. bolus+10 mg/kg/h for 4 h) reduced the volume of ischemic damage in the cerebral cortex in F344 rats. Thus, YM90K was shown to be a potent and selective antagonist for AMPA/kainate receptors in vitro and in vivo. This compound may provide a therapeutic effect in various neurodegenerative disorders such as ischemic stroke in which glutamate neurotoxicity is thought to play a critical role in neuronal damage.

Animals↗
PubMed1996

Effects of aluminum(III) on catechol-stimulated nerve growth factor biosynthesis by cultured mouse brain astroglial cells.

The effects of aluminum and other metal ions on the synthesis of nerve growth factor (NGF) by cultured mouse brain astroglial cells have been investigated. Natural NGF formation was dependent on the AlCl3 concentration of the cell culture medium; it was stimulated at low concentrations but was inhibited at higher concentrations. Catechol-stimulated NGF formation was also inhibited at AlCl3/catechol molar ratios > 0.3, whereas ZnCl2 and CaCl2 had no effect under similar conditions. Ethylenediamine-N,N,N',N'-tetraacetate (EDTA) and citrate blocked the inhibitory effect of Al(III). These observations were explained by the complex formation between Al(III) and catechols.

Aluminum↗
PubMed1995

Optical responses recorded after local stimulation in rat neostriatal slice preparations: effects of GABA and glutamate antagonists, and dopamine agonists.

Effects of GABA and glutamate antagonists as well as dopamine agonists and antagonists on the optical responses of neostriatal (Str) slices to local electrical stimulation were examined using a voltage-sensitive dye and a high-speed image sensor. A single local stimulation applied to the Str slices evoked optical responses lasting for 40-80 ms and propagating in every direction up to about 1.5 mm. Bath application of bicuculline methiodide increased the intensity and duration of optical responses, while their spatial response patterns were unchanged. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) greatly reduced the late part of responses occurring about 4 ms after stimulation, but the early part of responses was unaffected by CNQX. The early part of the response was eliminated by application of tetrodotoxin. Bath application of N-methyl-D-aspartate antagonists, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid resulted in only small changes in the optical responses. Bath application of D1 agonist 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benz aze pine hydrobromide consistently increased the intensity but decreased the speed of propagation and duration of the optical response. Bath application of D2 agonist quinpirole had no effect on the optical response. D1 antagonist SCH 23390 and D2 antagonist sulpiride also failed to change optical responses. These results indicate that the early part of the response is due to direct activation of the neuronal elements by electrical stimulation, while the late part of the response is due mainly to glutamatergic ex-citatory postsynaptic potentials (EPSPs) mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors. This study also suggests that dopamine may modulate AMPA/kainate responses through D1 receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

New 1,4-benzodiazepin-2-one derivatives as gastrin/cholecystokinin-B antagonists.

A novel series of 1-aroylmethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivatives was prepared and evaluated for activity as gastrin/cholecystokinin (CCK)-B receptor antagonists. In vitro binding studies showed that some derivatives exhibited potent affinity for gastrin CCK-B receptor and high selectivity over peripheral CCK(CCK-A) receptor. Furthermore these compounds potently inhibited pentagastrin-induced gastric acid secretion upon intravenous administration in an in vivo model in rats. Structure-activity relationship studies of this series suggested that 1-[(R)-2,3-dihydro-1-(2,3-dihydro-1-(2-methylphenacyl)-2-oxo-5-phe nyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (35b, YM022) was the optimal compound with IC50 values of 0.17, 0.11 and 150 nM for gastrin, CCK-B and CCK-A receptors, respectively, and an ED50 value of 9.5 nmol/kg (i.v.) in rats. The absolute configuration of the precursor of YM022, an (R)-3-amino-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivative ((R)-25), was determined by X-ray crystallographic analysis of its (S) mandelate. It would be expected that YM022, a potent and selective gastrin CCK-B receptor antagonist, inhibits gastric acid secretion without inducing gastrin-mediated side effects such as hypergastrinemia and hyperplasia of oxyntic mucosa.

Anesthetics↗
PubMed1994

Horizontal propagation of excitation in rat visual cortical slices revealed by optical imaging.

Optical imaging with high spatial and temporal resolution of neural activity in rat cortical slices was used to investigate the dynamics of signal transmission through neural connections in the visual cortex. When inhibition due to gamma-aminobutyric acid was slightly suppressed, horizontal propagation of excitation in both the supra- and infragranular layers became prominent. This propagation was not affected by vertical cuts in either the supra- or infragranular layer, which suggests that excitation is at least partially conveyed horizontally by reciprocal vertical connections between neurons in these layers.

Animals↗
PubMed1994

Possible presence of the ATP-sensitive K+ channel in isolated spinal dorsal horn neurons of the rat.

The ATP-sensitive K+ channel (KATP channel) is a K+ channel inhibited by cytoplasmic ATP. It was originally found in cardiac cells and recently in neuronal cells. Here, we present evidence indicating that the KATP channel also exists in spinal dorsal horn neurons: membrane currents were recorded by whole-cell voltage-clamp in spinal dorsal horn neurons isolated from young rats. The outward current was augmented by KATP channel activators nicorandil and minoxidil and reduced by the blocker glibenclamide. This glibenclamide-induced change in the current was augmented when the intracellular ATP was lowered and the reversal potential was shifted according to the external K+ concentration.

Adenosine Triphosphate↗
PubMed1994

Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gamma in stimulating the production of nerve growth factor in fibroblasts.

A possible interaction between tumor necrosis factor-alpha (TNF) and other cytokines/growth factors in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. TNF's stimulatory activity on fibroblast NGF production was synergized by interleukin-1 alpha (IL-1 alpha), IL-1 beta and interferon-gamma (IFN-gamma), but was antagonized by transforming growth factor-beta (TGF-beta). The most remarkable synergistic effect was observed between TNF and IL-1 alpha/beta; as little as 0.003 ng/ml of IL-1 beta markedly enhanced TNF's stimulatory activity on NGF production in the cells. These findings reinforce the idea that TNF, in concert with IL-1 alpha/beta, plays an essential role in regulating the regeneration of peripheral nerves following injury through an indirect mechanism by which it stimulates NGF production in fibroblasts.

3T3 Cells↗
PubMed1994

6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) and related compounds: structure-activity relationships for the AMPA-type non-NMDA receptor.

A novel series of quinoxalinediones possessing imidazolyl and related heteroaromatic substituents was synthesized and evaluated for their activity to inhibit [3H]AMPA binding from rat whole brain. From the structure-activity relationships, it was found that the 1H-imidazol-1-yl moiety could function as a bioisostere for the cyano and nitro groups, and that 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione (11) showed the most potent activity for the AMPA receptor. Compound 11 was evaluated for selectivity versus other excitatory amino acid receptors, and its action against AMPA at its receptor in the rat striatum was characterized. These data showed that compound 11 was a selective antagonist for the AMPA receptor with a Ki value of 0.084 microM, being approximately equipotent with 2,3-dihydro-6-nitro-7-sulfamoylbenzo(f)quinoxaline (3) (NBQX; Ki = 0.060 microM). Compound 11 was also found to give protection against sound-induced seizure on DBA/2 mice at the minimum effective dose of 3 mg/kg ip (3; 10 mg/kg ip).

Acoustic Stimulation↗
PubMed1994

Optical imaging of the in vitro guinea pig piriform cortex activity using a voltage-sensitive dye.

The spatio-temporal patterns of signal processing in guinea pig piriform cortex (PC) slices were analyzed by optical imaging using a voltage-sensitive dye. Slices (400 microns thick) were cut in a plane parallel to the lateral olfactory tract and perpendicular to the cortical surface. In all the anterior PC and the majority of the posterior PC preparations, neural activity elicited by electrical stimulation of layer Ia propagated along the same layer, then it invaded into layers II and III and propagated along them. In addition to the above pattern, invasion of activity into the deeper area than layer III was observed in some posterior PC preparations. Real-time imaging of an active zone evoked by Ia shocks and its spatio-temporal behavior will contribute to resolving olfactory information processing.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

An evaluation of the accelerated expectation maximization algorithms for single-photon emission tomography image reconstruction.

We previously reported that brain single-photon emission tomography (SPET) images could be improved by using an attenuation coefficient map constructed with transmission data and the iterative expectation maximization (EM) algorithm. However, the conventional EM algorithm (CEM) typically requires 30-80 iterations to provide acceptable results, limiting its clinical applicability. Several methods have been proposed to accelerate the EM algorithm. The purpose of this study was to search for a practical method for accelerating the EM algorithm. The methods investigated here include the accelerated EM algorithm (ACEM) using additive correction, ACEM using multiplicative correction, and Tanaka's filtered iterative reconstruction method (FIR). These methods were assessed by simulated SPET studies of a phantom incorporating nonuniform attenuation and by reference to clinical brain SPET data. In the simulation studies, the above methods were evaluated by using three parameters (root mean square error, log likelihood value, and contrast recovery coefficient); the results showed that FIR had an advantage over other methods in terms of all parameters. The results obtained using the clinical data demonstrated that FIR could reconstruct acceptable images in only five iterations. These results show that FIR offers significant advantages over CEM or other ACEMs, indicating that FIR can make the EM algorithm practical for clinical use in SPET.

Adult↗
PubMed1994

Neurotrophin-3 (NT-3) levels in the developing rat nervous system and in human samples.

We developed an enzyme immunoassay (EIA) system for neurotrophin-3 (NT-3), based on a biotin-streptavidin detection system capable of measuring concentrations as low as 0.5 pg/ml with high reproducibility. We measured NT-3 levels in the developing rat nervous system as well as in normal subjects and patients with Alzheimer's disease (AD). The developmental change of NT-3 level in rat brain and peripheral tissues coincided with the change in NT-3 mRNA level reported before. We could not find any differences in NT-3 level in serum, cerebrospinal fluid, or brain (hippocampus and parietal cortex) obtained from controls and patients with AD.

Adult↗