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At least 811 records · Page 45Linked to original sources

PubMed1981

L-Tryptophan injection enhances pulsatile growth hormone secretion in the rat.

The effect of injecting L-tryptophan or a serotonin receptor agonist [6-Cl-2-[1-piperazinyl]pyrazine ((MK0212)] on pulsatile GH secretion was studied in male rats bearing right atrial cannulae. After injection, blood samples were drawn at 15-min intervals for periods up to 4 h. L-Tryptophan administration (50 or 100 mg/kg, ip) significantly enhanced mean plasma GH levels measured over a 3.5-h period. Injection of another large neutral amino acid, L-valine (100 mg/kg, ip), did not influence plasma GH levels. However, when administered with tryptophan, valine blocked the tryptophan-induced enhancement of GH secretion and blunted the increases in brain tryptophan and serotonin levels that normally accompany tryptophan injection. Injection of MK-212 (2 mg/kg, ip) elicited an immediate rise in plasma GH levels; this effect was completely blocked by pretreatment with metergoline (2 mg/kg, ip), a serotonin receptor antagonist. Taken together, these data support the notion that treatments which increase serotonin receptor stimulation enhance or induce pulsatile GH secretion.

Animals↗

PubMed2006

Effects of four Si-Wu-Tang's constituents and their combination on irradiated mice.

Effects of four Si-Wu-Tang (SWT)'s constituents, fructose (Fru), paeoniflorin (Pae), ferulic acid (FA), tetramethyl pyrazine (TP), and their combination on irradiated mice as model of anaemia were investigated, with the purpose of further understanding the relationship between SWT's constituents and activities. Similarly to SWT, oral administration of Fru, Pae, FA, TP and their combination, to some extent, all showed effects of increasing the number of peripheral leukocyte and increasing four types of progenitor cells in bone marrow, including colony-forming unit-granulocyte-macrophage (CFU-GM), colony-forming unit-mature erythroid (CFU-E), colony-forming unit-immature erythroid (BFU-E) and colony-forming unit-multipotential (CFU-mix). Pae and FA showed significant body weight reducing effect, which were largely abolished when they were combined with Fru and TP. The SWT, Fru and combination significantly increased the thymus index while Pae significantly decreased it. Both SWT and TP significantly increased the spleen index but the combination did not. The results suggested that multiple constituents contribute to the promoting effect of SWT on hematopoiesis. Although being a very common compound in plants, the Fru has a special contribution to SWT's effect, which cannot be neglected. It may be an important active constituent that is responsible for SWT's promoting effect on hematopoiesis and immunity. Another suggestion is that when being combined, some effect of one constituent, sometimes is unexpected side effect, may be abolished by other. This may reflect the advantage of multiple constituent characteristics possessed by most TCMs.

Animals↗

PubMed1990

Studies on antiallergic agents. II. Quantitative structure-activity relationships of novel 6-substituted N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamides.

The effect of structural modifications of 6-substituted N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamides on their anti-allergic activity was analyzed quantitatively by means of the Hansch-Fujita method. The activity of these compounds was correlated with hydrophobic (pi) and steric (molecular refractivity and STERIMOL B1) effects of the 6-substituent on the pyrazine ring. The 6-substituents with a length greater than n-propylamino possess an extra effect enhancing the activity. Moreover, the activity increased progressively from 6-non-amino via alkylamino- to dialkylamino-substituted compounds, other factors being equal. This could be attributable to an electronic effect of substituents. Electron-donating small and yet symmetric substituents with high hydrophobicity longer than n-propylamino seemed to be favorable to the activity. By compromising these contradictory requirements, small dialkylamino (including cyclic amino) groups were decided to be the most favorable substituents. This analysis was in agreement with the observation that the most effective compounds were the 6-dimethylamino (I-27) and 6-(1-pyrrolidinyl) (I-34) derivatives.

Animals↗

PubMed2002

Hydrophobicity parameters determined by reversed-phase liquid chromatography. XV: optimal conditions for prediction of log P(oct) by using RP-HPLC procedures.

The use of log k derived from reversed phase (RP)-HPLC retention times provides a convenient method for estimating log P(oct) values (P(oct): 1-octanol/water partition coefficient). In order to establish optimal HPLC conditions, the difference between chromatographic (C18 modified column and aqueous methanol eluents) and bulk solvent systems was examined by use of a batch-like equilibration with octane/aqueous methanol. Comparison of values for log P(O/M-W) (log P for the Octane/MeOH-Water partitioning system) and log k measured for monosubstituted pyrazines at different methanol concentrations, showed closest correlation (r, 0.94) with 50% aqueous methanol; and importantly, under these conditions, log k shows even better correlation (r, 0.99) with log P(oct). Effects of residual silanols on HPLC retention with C18 stationary phases were examined. The results show that, in the presence of a small quantity of accessible silanols, the use of 50% aqueous methanol (M50) as eluent yields values of log k directly proportional to log P(oct) in accord with our earlier proposal that use of log k(M50) provides a convenient means for rapid estimation and prediction of log P(oct).

Chromatography, High Pressure Liquid↗

PubMed2004

[Chemical profiles of methylpyrazines contained in commercially available natto].

Structures and amounts of methylpyrazines contained in commercial natto, a fermented soybean food in Japan, were determined using HPLC equipped with an acid-resistant reversed phase column, Capcell Pak C18 ACR (Shiseido). Mobile phase solvent mixtures consisted of acidic phosphate buffer solution (pH 2.0) containing 2% acetonitrile gave satisfactory results with baseline separation of the authentic specimens, such as naked pyrazine, monomethylpyrazine, 2,3-, 2,5-, and 2,6-dimethylpyrazine, trimethylpyrazine, and tetramethylpyrazine. We used the mobile-phase solvent with a flow rate of 1 ml/min at 15.0 degrees C. Before HPLC, commercial natto samples were treated with water to prepare diluted suspensions of surface mucous materials. The suspensions were treated on Sep-Pac C18 Cartridges (Waters) with phosphate buffer solutions containing 2-7% acetonitrile. The extracts were then injected into the analytical column to obtain chromatograms that were used to determine the structures and amounts of methylpyrazines. The results showed that a commercialiy packed natto contains a considerable amount of 2,5-dimethylpyrazine instead of the tetrametyl- and trimethylpyrazines in the traditional products. This may be a result of recent efforts of natto makers whose interests have been focused on new methods for preparing odorless products.

Chromatography, High Pressure Liquid↗

PubMed2001

Continuous observation of superoxide generation in an in-situ ischemia-reperfusion rat lung model.

To investigate the time course of superoxide generation in ischemia-reperfusion in the in-vivo rat lung, the present study used an enhanced chemiluminescence method with 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1, 2-alpha]pyrazin-3-one (MCLA) as a specific probe. The right pulmonary artery was occluded for 120 min, followed by 90-min reperfusion. Chemiluminescence induced by MCLA was continuously monitored by a photomultiplier exposed to the right lung. Chemiluminescence increased gradually in 30 min of reperfusion and remained elevated throughout reperfusion. The ratio of the luminescence count during reperfusion to the preischemic value increased to 2.20+/-0.31 (mean+/-SEM) (p<0.02 vs preischemic level), 2.50+/-0.39 (p<0.005), and 2.69+/-0.44 (p<0.005), at 30, 60, and 90 min of reperfusion, respectively. Bolus administration of superoxide dismutase during the reperfusion period significantly attenuated the chemiluminescence by 45.0+/-6.7% (p<0.01). The present results suggest that increasing oxygen radical formation leading to ischemia-reperfusion lung injury may occur even after a short period of occlusion of the pulmonary artery alone in vivo.

Animals↗

PubMed1997

Generation of reactive oxygen species by raphidophycean phytoplankton.

Chattonella marina, a raphidophycean flagellate, is one of the most toxic red tide phytoplankton and causes severe damage to fish farming. Recent studies demonstrated that Chattonella sp. generates superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH), which may be responsible for the toxicity of C. marina. In this study, we found the other raphidophycean flagellates such as Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica also produce O2- and H2O2 under normal growth condition. Among the flagellate species tested, Chattonella has the highest rates of production of O2- and H2O2 as compared on the basis of cell number. This seems to be partly due to differences in their cell sizes, since Chattonella is larger than other flagellate species. The generation of O2- by these flagellate species was also confirmed by a chemiluminescence assay by using 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA). All these raphidophycean flagellates inhibited the proliferation of a marine bacterium, Vibrio alginolyticus, in a flagellates/bacteria co-culture system, and their toxic effects were suppressed by the addition of superoxide dismutase (SOD) or catalase. Our results suggest that the generation of reactive oxygen species is a common feature of raphidophycean flagellates.

Animals↗

PubMed1995

Factors involved in the N-oxidation of isomeric aromatic diazines by microsomal preparations.

Factors affecting the metabolism of isomeric aromatic diazines in vitro were studied and the conditions which allow maximal metabolism established. The N-oxidation of isomeric diazines was linear with respect to microsomal concentration up to 0.5 g original liver weight per ml using a rabbit microsomal suspension. N-Oxidation was also linear up to between 20-30 minutes depending on substrate studied. The rate of N-oxide production increased with increase in substrate concentration up to about 10 mumol/incubate, after which the rate declined. By using the data obtained the appropriate kinetic factors, Km and Vmax, for the N-oxidation of pyrazine, pyrimidine and pyridazine by rabbit hepatic microsomal preparations were calculated. Spectral binding constants, Ks, of substrates to cytochrome P450 were also calculated and appeared to be related to the Km values.

Animals↗

PubMed1997

Continuous detection of superoxide in situ during ischemia and reperfusion in the rabbit heart.

In order to clarify the time course of superoxide generation in situ during ischemia and reperfusion in the rabbit heart, we used a method of enhanced chemiluminescence (CL) with 2-methyl-6-[p-methoxyphenyl]-3, 7-dihydroimidazo [1, 2-alpha]pyrazin-3-one (MCLA) as a specific probe for detecting superoxide radicals. The surface of the rabbit heart was exposed to a photomultiplier tube in a light-proof box. We introduced a reversible snare occluder into the box to continuously observe the light emission. An ischemia-reperfusion group (I/R, n = 7) was subjected to 30 mins of coronary occlusion, followed by 90 mins of reperfusion. We performed the same procedure (except for coronary occlusion) in the sham-operated group (n = 4). Another group of rabbits (n = 4) subjected to I/R received superoxide dismutase (SOD: 20 mg/kg, i.v.) during reperfusion to observe the CL response. In the I/R-group, the increase in CL began at 13 +/- 2 (mean +/- SEM) mins and peaked at 52 +/- 12 mins of reperfusion. CL in the I/R-group gradually increased from 818 +/- 350 counts/10 secs in the preischemic period to 1077 +/- 401 counts/10 secs during reperfusion (p < 0.01). In contrast, there was no increase in CL in the sham-operated group. The administration of SOD briefly attenuated CL by 24.1 +/- 6.8% for a period of 24.3 +/- 6.8 mins. The superoxide generation in situ in the ischemic rabbit heart appears to increase gradually and persists for a period following reperfusion.

Animals↗

PubMed2003

Reestimation of Cypridina luciferin analogs (MCLA) as a chemiluminescence probe to detect active oxygen species--cautionary note for use of MCLA.

Cypridina luciferin analogs have been widely used as a specific chemiluminescence probe for the detection of superoxide anion (O2-) and singlet oxygen (1O2). However, light emission during the reaction of Cypridina luciferin analogs and other active oxygen species (AOS) has not been reported in detail. Therefore, we re-evaluated 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazine-3-one (MCLA), one of the Cypridina luciferin analogs, as a chemiluminescence probe to detect various AOS. MCLA-dependent chemiluminescence was observed when MCLA was incubated with the following systems; 1) hypoxanthine plus xanthine oxidase (O2-), 2) thermolysis of endoperoxide (1O2), 3) hydrogen peroxide plus ferrous ion (hydroxyl radical), 4) ferrous ion, 5) thermolysis of azo compound (alkyl peroxyl radical) and 6) hydrogen peroxide. Superoxide dismutase inhibited MCLA-dependent chemiluminescence observed during ferrous ion-induced decomposition of hydrogen peroxide. Alkyl peroxyl radical reacted with MCLA, but light was not emitted when the concentration of MCLA was high. These results suggest that radicals, except O2-, appeared not to be direct inducers of MCLA-dependent light emission. In summary, MCLA-dependent chemiluminescence was induced by various AOS in addition to O2- and 1O2, but active species must be O2- and 1O2 in many cases. These points should be appreciated when Cypridina luciferin analogs, such as MCLA, are used for the detection of AOS.

Free Radicals↗

PubMed2002

In vivo measurement of superoxide in the cerebral cortex during anoxia-reoxygenation and ischemia-reperfusion.

Abstract. The exact time profile of superoxide generation during anoxia-reoxygenation and ischemia-reperfusion was assessed in the feline cerebral cortex in vivo using a chemiluminescence technique with a probe specific for superoxide, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA). MCLA solution was superfused on the cortex throughout the protocol, and MCLA chemiluminescence was measured using a newly developed photon counting system. Reflectance at 398 nm was simultaneously measured to compensate for hemodynamic artifacts resulting from cerebral blood volume changes. In 19 animals, a 90-second anoxia was induced by the inhalation of 100% nitrogen followed by a 40-minute reoxygenation. The chemiluminescence decreased during the period of anoxia (p < 0.01) and then exceeded the baseline level at 15 and 20 minutes after reoxygenation (p < 0.05). In six animals, superoxide dismutase (SOD) was continuously superfused and anoxia-reoxygenation was performed in the same manner. The chemiluminescence decreased during the period of anoxia (p < 0.05) but did not exceed the baseline level during the reoxygenation period, indicating that an increase in superoxide production was the main cause of the chemiluminescence increase. In eight animals, a 15-minute forebrain ischemia was induced by the occlusion of the bilateral common carotid arteries with systemic hypotension (systolic blood pressure less than 50 mmHg) followed by a 30-minute reperfusion. The chemiluminescence decreased during the period of ischemia (p < 0.01) and then increased at 20 and 25 minutes after reperfusion (p < 0.05). These results indicate that superoxide generation decreases during anoxia and ischemia and then increases within 20 minutes after reoxygenation or reperfusion.

Animals↗

PubMed1992

Mercapturic acid formation from 2-aminopyrazine in rats.

1. The compound 2-aminopyrazine was given by oral gavage to normal rats and their urine collected. 2. A mercapturic acid containing the 2-aminopyrazine moiety was isolated from this urine. This represents the first example of this type of a metabolite from a pyrazine.

Acetylcysteine↗

PubMed1996

Effect of various potential inhibitors, activators and inducers on the N-oxidation of isomeric aromatic diazines in vitro using rabbit liver microsomal preparations.

1. The effects of various potential inhibitors, activators and inducers on the N-oxidation of isomeric aromatic diazines (pyrazine, pyrimidine and pyridazine) by rabbit liver microsomes have been studied. 2. 2,4-Dichloro-6-phenylphenoxyethylamine (DPEA), SKF 525-A and N-octylamine decreased N-oxide formation at 10(-4) M concentrations. 3. Methimazole and carbon monoxide inhibited the N-oxidation of all three substrates studied. 4. The inhibitory effects were generally exaggerated when hepatic microsomal preparations from phenobarbitone-pretreated animals were used as enzyme source. 5. When phenobarbitone or pyridine were used as inducing agents, the N-oxidation of isomeric aromatic diazines showed considerable induction, whereas beta-naphthoflavone and Arochlor 1254 pretreatment had much weaker effects. 6. It is suggested that P4502E1 and/or 2B are the major subfamilies of P450 involved in the N-oxidation of isomeric diazines.

Animals↗

PubMed2002

Amelioratory effect of barley tea drinking on blood fluidity.

Effects of barley tea drinking on blood fluidity were evaluated by measuring the passage time of whole blood with a microchannel array flow analyzer (MC-FAN). The ingestion of barley tea in 250 mL amounts decreased the passage time of whole blood, but this did not occur with the ingestion of the same volume of water. 2,3,5-Trimethyl pyrazine at the same level as in barley tea also caused a significantly decreased time of blood passage in vitro. This suggests that alkylpyrazines may serve as factors affecting the blood fluidity in barley tea drinking.

Adult↗

PubMed1991

Novel inhibitors of superoxide anion generation, OPC-15160 and OPC-15161. Taxonomy, fermentation, isolation, physico-chemical properties, biological characteristics and structure determination.

A new inhibitor of superoxide anion generation by guinea pig macrophages, OPC-15160, was isolated from the culture broth of fungus Thielavia minor OFR-1561, and a more potent inhibitor, OPC-15161, was obtained as a major degradation product of OPC-15160. OPC-15161 was five times more active than the natural inhibitor and its IC50 value was 2.8 x 10(-5) M. The structure of OPC-15161 was elucidated by X-ray analysis to be 6-(1H-indol-3-ylmethyl)-5-methoxy-3- (2-methylpropyl)-2-(1H)-pyrazinone, 4-oxide and had a novel and highly functionalized pyrazine skeleton.

Animals↗

PubMed2001

RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists are of potential interest for the treatment of certain acute and chronic neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we describe the synthesis and pharmacological properties of 9-carboxymethyl-4-oxo-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonic acid (RPR 119990). The compound displaced [3H]AMPA from rat cortex membranes with a K(i) of 107 nM. In oocytes expressing human recombinant AMPA receptors, RPR 119990 depressed ion flux with a K(B) of 71 nM. The antagonist properties of this compound were confirmed on rat native AMPA receptors in cerebella granule neurons in culture and in hippocampal slices where it antagonized electrophysiological responses with IC50 values of 50 and 93 nM, respectively. RPR 119990 antagonized hippocampal evoked responses in vivo, demonstrating brain penetration at active concentrations. RPR 119990 is a potent anticonvulsant in the supramaximal electroshock in the mouse with an ED50 of 2.3 mg/kg 1 h post s.c. administration, giving it a workably long action. Pharmacokinetic studies show good passage into the plasma after subcutaneous administration, whereas brain penetration is low but with slow elimination. This compound was found active in a transgenic mouse model of familial amyotrophic lateral sclerosis (SOD1-G93A) where it was able to improve grip muscle strength and glutamate uptake from spinal synaptosomal preparations, and prolong survival with a daily dose of 3 mg/kg s.c.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Detection of vitamin C-induced singlet oxygen formation in oxidized LDL using MCLA as a chemiluminescence probe.

In this study, it was observed that addition of vitamin C (vit C) to oxidized low-density lipoprotein (Ox-LDL) by cupric ions (Cu2+) could result in the formation of singlet oxygen (1O2). In experiments, 1O2 was detected by chemiluminescence method using a Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3, 7-dihydroimidazo [1, 2-a] pyrazin-3-one (MCLA), as a selective and sensitive chemiluminescence probe. Additional experimental evidence for the formation of 1O2 came from the quenching effect of sodium azide (NaN3) on vit C-induced chemiluminescence in the reaction mixture of LDL-Cu(2+)-MCLA. Analysis based on the experimental results demonstrated the plausible reaction mechanism is that vit C first converts Cu2+ to its reduced state and vit C becomes vit C radical itself, thereby stimulating the formation of peroxyl and alkoxyl radicals, and bimolecular reaction of peroxyl radicals results in 1O2 production in the systems studied.

Ascorbic Acid↗

PubMed1992

Oxiradical-dependent photoemission induced by a phacoemulsification probe.

Oxygen free radical formation by conventional phacoemulsification devices has been postulated as a possible mechanism of corneal endothelial damage during surgery. To test this hypothesis, phacoemulsification probe-induced free radical production was visualized using a single photon-counting camera and an O(2-)-sensitive luciferin derivative, 2-methyl-6-[p-methoxyphenyl-3,7-dihydroimidazo [1,2-a]pyrazin-3-one (MCLA), which allows the visualization of spatial and temporal alterations in free radical production. Within 1 min after starting ultrasound emission, MCLA-dependent chemiluminescence was increased significantly, the intensity of which was maximal at the tip of the probe and tapered along a gradient toward distal portions. The chemiluminescence was suppressed significantly by adding either superoxide dismutase (300 U/ml) or sodium azide (20 mmol/l). By adding deuterium to the medium, MCLA-dependent chemiluminescence significantly increased, suggesting the involvement of singlet oxygen in the reaction.

Azides↗