bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACTIVATORS and INHIBITORS OF BRAIN GLUTAMINASE
Authors: Weil‐Malherbe H. 
Published: October 2006

Abstract—(1) The glutaminase activity of a guinea pig brain dispersion (a 1500g supernatant solution) was tested at pH 7.5 in the presence of a series of organic acids at 20 mm with or without the further addition of 7.5 mm‐phosphate.(2) In the absence of phosphate, glutaminase activity was strongly enhanced by tricarboxylic acids, less strongly by dicarboxylic acids, and slightly, if at all, by monocarboxylic acids. Acidic amino acids were intermediate between mono‐ and dicarboxylic acids. In the presence of 7.5 mm‐phosphate, the addition of 20 mm organic acids resulted in strong potentiation of the activating effect in many cases. The activating effect of even the most active of the organic acids tested, citrate, was only about half of the effect of an equimolar amount of phosphate.(3) At phosphate concentrations approaching the saturation level for activation, the further addition of citrate was without effect.(4) Glutaminase was strongly activated by ITP which was about three times as active as inorganic phosphate. IMP was less active than inorganic phosphate and creatine phosphate had only slight activity which seemed to be accounted for by its content of inorganic phosphate.(5) Glutaminase was activated by fluoride, in the presence as well as in the absence of added phosphate. Chloride, bromide, and iodide, at 100 mm, produced increasing inhibition of the phosphate‐activated reaction. The inhibiting effect of iodide was qualitatively competitive with phosphate.(6) The effects of various other potential inhibitors and activators, including SH‐reagents, d‐glutamine, several amino acids, and amino acid derivatives were studied.(7) The results have been discussed with particular reference to their significance in elucidating the natural function of brain glutaminase. It has been suggested that glutaminase is an allosteric enzyme and that the secondary active site requires a reaction with three anionic groups for full activation.
HYDROLASE ACTIVITIES IN BRAIN OF NEUROLOGICAL MUTANTS: CEREBROSIDE GALACTOSIDASE, NITROPHENYL GALACTOSIDE HYDROLASE, NITROPHENYL LUCOSIDE HYDROLASE AND SULPHATASE1
Authors: Bowen D. M. , Radin N. S. 
Published: October 2006

Abstract—

The brains of 17‐day‐old quaking and jimpy mice were compared with those of the corresponding normal phenotypes. The concentrations of cerebroside and sulphatide were found to be markedly lower in the affected mutants, while the relative amounts of ceramide and free fatty acid appeared normal.
The concentration of cerebroside glactosidase was not significantly abnormal in the jimpy mice but was about 17 per cent lower in quaking mice. In contrast, the relative amount of the enzyme that could be dispersed by sonication was considerably higher in the jimpy animals. It is suggested that this increase is a causative factor in the aetiology of the latter disease.
The concentrations of other acid hydrolases were determined, as well as the relative amounts dispersible by sonication. No difference was seen between the phenotypes with NPGalH, NPGluH, and nitrocatechol sulphate hydrolase.
An improved solvent system for the TLC detection of ceramide in brain lipids is described.
MERCAPTOPROPIONIC ACID: A CONVULSANT THAT INHIBITS GLUTAMATE DECARBOXYLASE1
Authors: Lamar C. 
Published: October 2006

Abstract—3‐Mercaptopropionic (MP) and 4‐mercaptobutyric (MB) acids caused convulsions in rats after the intraperitoneal administration of 32 and 200 mg/kg body wt. respectively. These compounds competitively inhibited glutamate decarboxylase (L‐glutamate 1‐carboxy‐lyase; EC 4.1.1.15) of rat brain and bacterial GABA transaminase (4‐aminobutyrate: 2‐oxoglutarate aminotransferase; EC 2.6.1.c). Glutamine synthetase (L‐glutamate: ammonia ligase (ADP); EC 6.3.1.2) was not affected. Pyridoxal phosphate added in vitro did not reverse the inhibition. Action of these compounds is compared to methionine sulphoximine, a bacterial exotoxin (lactylaminopimelic acid) and to hydrazinopropionic acid.
CEREBRAL PROTEINASES IN THE GROWING RAT1
Authors: Oja S. S. , Oja Hely 
Published: October 2006

Abstract—The proteolytic activity of brain homogenates obtained from 1‐, 5‐, 14‐, 60‐, 150‐, and 300‐day‐old rats was assayed with urea‐denatured haemoglobin and casein, endogenous tissue proteins, Nα‐benzoyl‐dl‐arginine 2‐naphtylamide (BANA), Nα‐benzoyl‐dl‐arginine methyl ester (BAME), Nα‐toluene p‐sulphonyl‐dl‐arginine methyl ester (TAME), Nα‐benzoyl‐dl‐phenylalanine 2‐naphthyl ester (BPANE), and Nα‐acetyl‐dl‐tyrosine ethyl ester (ATEE) as substrates.Several peaks of activity were detected with all these substrates in different pH ranges. Activity was highest with protein substrates at pH 3·0‐4·0, with smaller peaks of activity at pH 5·5‐6·5 and 8·0‐9·0. At pH 3·0 the activity with trypsin substrates, viz. BANA, BAME and TAME, was also relatively high, but much less with chymotrypsin substrates, ATEE or BPANE. With BAME, TAME, BPANE and ATEE the hydrolysis rate was highest at neutral or slightly alkaline pH. During postnatal development the hydrolysis of protein substrates increased three‐fold at pH 3·0 and about two‐fold at pH 6·5 and 8·5. The rate of hydrolysis of BANA, BAME and TAME generally increased during the first 2 postnatal weeks and thereafter decreased, whereas no marked increase in the rate of hydrolysis of BPANE and ATEE occurred until the age of about 2 weeks. The results were less consistent with synthetic substrates than with protein substrates, indicating the existence of non‐uniform alterations during development in the activity of the individual hydrolytic enzymes participating in the breakdown of brain proteins.
THE PROTEIN COMPOSITION OF ISOLATED MYELIN1
Authors: Gonzalez‐Sastre F. 
Published: October 2006

Abstract—Three fractions, each containing markedly different proteins, was obtained from myelin:(1) The first fraction was obtained as an insoluble residue when myelin was extracted with neutral chloroform‐methanol (CM, 2:1, v/v). It was digestible with trypsin and had an amino acid composition similar to that of the acidic proteolipid protein of Wolfgkam (1966).(2) The second fraction was obtained as a precipitate by the addition of various electrolytes (KCl, NaCl, CaCl2, MgCl2 or HCl) to the CM (2:1 v/v) extract. This fraction consisted mainly of a basic protein which exhibited an electrophoretic mobility and amino acid composition indistinguishable from those of the basic protein obtained from white matter (Martensson and LeBaron, 1966). This procedure provided for a simple and rapid isolation of the basic protein from myelin. Depending on the conditions of precipitation, this fraction was either free of lipid or contained tri‐ and diphosphoinositide. The effects of different ions at differing concentrations and the yield and nature of the precipitate have been studied.(3) A third fraction remained in solution in CM (2:1, v/v) after the addition of the electrolyte. It comprised the bulk of the myelin lipids and a protein fraction which was resistant to digestion with trypsin and had an amino acid composition similar to the classical proteolipid protein of Folch‐Pi and Lees (1951).The possibility of a salt‐type bonding between the basic protein and the polyphosphoinositides is discussed, and values for tri‐ and diphosphoinositide in bovine myelin are given.
QUANTITATIVE HISTOCHEMISTRY OF ACETYL‐CHOLINESTERASE IN RAT HIPPOGAMPAL REGION CORRELATED TO HISTOCHEMICAL STAINING
Authors: Storm‐Mathisen J. 
Published: October 2006

Abstract— The quantitative histochemistry of acetylcholinesterase (AChE) has been examined in hippocampus (regio superior) and area dentata. Samples (0–05–2 μg) were dissected from freeze‐dried tissue sections and assayed by either a colorimetric or a radiometric micromethod. In hippocampus the highest AChE activity occurred in a narrow zone just beneath the layer of pyramidal cells. Stratum oriens had a higher activity than stratum radiatum. A small peak of activity occurred in the lacunosal layer. In area dentata the overall activity was about 60 per cent higher than in the hippocampus. The highest activities were found in two zones adjacent to the granular layer.When the results were expressed as activities per volume of tissue they correlated well with microdensitometric measurements on sections stained for AChE by the Koelle method.Following transection of the fimbria the activity decreased to a low level, approaching a common value in the layers examined.The results are discussed in relation to the significance of AChE in the hippocampal region.
FATTY ACID COMPOSITION OF CEREBROSIDES, SULPHATIDES AND CERAMIDES IN MURINE SUDANOPHILIC LEUCODYSTROPHY: THE JIMPY MUTANT
Authors: Joseph K. C. , Hogan E. L. 
Published: October 2006

AbstractThe fatty acid composition of cerebrosides, sulphatides and ceramides was determined at 15‐16 days post partum in the brain of the Jimpy mutant and in littermate controls. There was a marked deficit in the long chain fatty acids (C22‐C24) of cerebrosides and sulphatides of Jimpy brain, with the unsubstituted fatty acids affected more than the alpha‐hydroxy fatty acids. A decrease of long chain normal fatty acids was also found in the ceramides of Jimpy brain. The deficit of long chain fatty acids in these sphingolipids of the Jimpy brain was more severe than that found in the Quaking mutant which has a less extensive disorder of myelin formation.
DISTRIBUTION OF TYROSINE HYDROXYLASE IN HUMAN AND ANIMAL BRAIN1
Authors: McGeer E. G. , McGeer P. L. , Wada J. A. 
Published: October 2006

AbstractThe activity of tyrosine hydroxylase (EC 1.10.3.1) when assayed under ideal conditions in young human brains, was comparable to that in brains of other species in level of activity and distribution. The highest levels of activity were in the putamen, caudate nucleus and substantia nigra, in keeping with data on other species. The caudate activity in human brain appeared to decrease substantially with increasing age. In both humans and baboons, the enzyme in the neostriatum was particle‐bound and inhibited by the 2‐amino‐4‐hydroxy‐6,7‐dimethyltetrahydropteridine cofactor system. In the substantia nigra it was soluble and stimulated by the 2‐amino‐4‐hydroxy‐6,7‐dimethyltetrahydropteridine cofactor system. The data suggest that tyrosine hydroxylase may be produced in a soluble form in the cell bodies of the substantia nigra but become bound as it moves toward the nerve endings in the putamen and caudate nucleus. The bound form of the enzyme was unstable but the soluble form exhibited considerable stability.
THE EFFECT OF PHOSPHOLIPASE C ON THE ACTIVITY OF ADENOSINE TRIPHOSPHATASE AND ACETYLCHOLINESTERASE IN SYNAPTIC MEMBRANES ISOLATED FROM THE CEREBRAL CORTEX OF SQUIRREL MONKEY1
Authors: Sun A. Y. , Sun G. Y. , Samorajski T. 
Published: October 2006

AbstractA synaptic‐membrane fraction rich in junctional components and Na‐K ATPase and AChE activity was isolated from the cerebral cortex of the squirrel monkey. Incubation of membrane preparations with phospholipase C decreased the activity of Na‐K ATPase by 50 per cent but had no effect on the activity of AChE. Analysis of the membrane fraction showed that phospholipase C cleaved both choline phosphoglyceride and the diacyl type of ethanolamine phosphoglyceride from membrane lipids. Addition of egg lecithin at low concentrations partially restored the activity of Na‐K ATPase. Kinetic studies revealed that treatment with phospholipase C may produce a non‐competitive type of inhibition as a result of the cleavage of a charged phosphorylated nitrogen base from membrane lipids.
ACTIVATION OF PIG BRAIN GLUTAMINASE
Authors: Svenneby Gerd 
Published: October 2006

AbstractPig brain glutaminase (EC 3.5.1.2, l‐glutamine amidohydrolase) is activated by certain anions (e.g. phosphate, fluoride, carboxylic acids) and inhibited by others (e.g. chloride, bromide, iodide and glutamate). The only cation which has been found to activate the enzyme is the ammonium ion. This applies to both the tris‐HCl form and the phosphate‐borate form of glutaminase.
THE STRUCTURAL SPECIFICITY OF THE HIGH AFFINITY UPTAKE OF l‐GLUTAMATE AND l‐ASPARTATE BY RAT BRAIN SLICES
Authors: Balcar V. J. , Johnston G.A. R. 
Published: October 2006

Abstract— The high affinity uptake system for l‐glutamate and l‐aspartate in rat cerebral cortex may not be specific for these likely excitatory synaptic transmitters, as threo‐3‐hydroxy‐dl‐aspartate, l‐cysteinesulphinate, l‐cysteate and d‐aspartate strongly inhibit the observed high affinity uptake of l‐[3H]glutamate by rat brain slices in a manner consistent with linear competitive inhibition. These substances should therefore be considered as possible substrates for the transport system. Each of these four acidic amino acids excites central neurones in a manner similar to excitation induced by l‐glutamate, and as each might occur in brain tissue, their possible synaptic role should be investigated. l‐Glutamate high affinity uptake was shown to be sodium‐dependent, but under certain conditions appeared to be less sensitive than GABA uptake to changes in the external sodium ion concentration, and to drugs which modify sodium ion movements. This may be relevant to the efficiency of the glutamate uptake process during synaptic depolarization induced by glutamate. l‐Glutamate high affinity uptake was inhibited in a relatively nonspecific manner by a variety of drugs including mercurials and some electron transport inhibitors.
CEREBRAL CARBOHYDRATE METABOLISM DURING ACUTE HYPOXIA AND RECOVERY1
Authors: Duffy T. E. , Nelson S. R. , Lowry O. H. 
Published: October 2006

Abstract— The levels of ATP, ADP, AMP and phosphocreatine, of four amino acids, and of 11 intermediates of carbohydrate metabolism in mouse brain were determined after: (1) various degrees of hypoxia; (2) hypoxia combined with anaesthesia; and (3) recovery from severe hypoxia. Glycogen decreased and lactate rose markedly in hypoxia, but levels of ATP and phosphocreatine were normal or near normal even when convulsions and respiratory collapse appeared imminent.During 30 s of complete ischaemia (decapitation) the decline in cerebral ATP and phosphocreatine and the increase in AMP was less in mice previously rendered hypoxic than in control mice. From the changes we calculated that the metabolic rate had decreased by 15 per cent or more during 30 min of hypoxia.Hypoxia was also associated with decreases of cerebral 6‐phosphogluconate and aspartate, and increases in alanine, γ‐aminobutyrate, α‐ketoglutarate, malate, pyruvate, and the lactate :pyruvate ratio. Following recovery in air (10 min), increases were observed in glucose (200 per cent), glucose‐6‐phosphate, phosphocreatine and citrate, and there was a fall in fructose‐1, 6‐diphosphale.Similar measurements were made in samples from cerebral cortex, cerebellum, midbrain and medulla. Severe hypoxia produced significant increases in lactate and decreases in glycogen in all areas; γ‐aminobutyrate levels increased in cerebral cortex and brain stem, but not in cerebellum. No significant changes occurred in ATP and only in cerebral cortex was there a significant fall in phosphocreatine.Phosphocreatine, ATP and glycogen were determined by quantitative histochemical methods in four areas of medulla oblongata, including the physiological respiratory centre of the ventromedial portion. After hypoxia, ATP was unchanged throughout and the changes (decreases) in phosphocreatine and glycogen were principally confined to dorsal medulla, notably the lateral zone.Thus there is no evidence that respiratory failure is caused by a ‘power’ failure in the respiratory centre. It is suggested that in extremis a protective mechanism may cause neurons to cease firing before high‐energy phosphate stores have been exhausted.
EFFECTS OF METABOLIC INHIBITORS ON THE RELEASE OF GLUTAMATE FROM THE RETINA1
Authors: Harreveld A. Van , Fifkova Eva 
Published: October 2006

Abstract—The superfused, isolated retina of the chicken was used to investigate the mechanisms responsible for the increase in retinal transparency and the release of glutamate associated with stimuli known to elicit spreading depression (SD). We sought to distinguish between (1) mechanisms involving glutamate‐induced increase in Na+ permeability and consequent uptake of extracellular material into the intracellular compartment and (2) mechanisms involving interference with operation of the Na+ pump that would result in a similar uptake of extracellular materials. Tetrodotoxin (which inhibits inward movements of Na+) depressed the transparency increase caused by stimulation with glutamate but not that elicited by application of KCl. Ouabain (which inhibits the Na+ pump) caused a marked increase in tissue transparency. The application of inhibitors of the aerobic metabolism, such as DNP or cyanide, or deprivation of O2 had no effect on the retinal transparency; results suggesting that the energy for the Na+ pump could be supplied by glycolysis. Indeed iodoacetate (which inhibits glycolysis) caused a marked change in transparency. Furthermore we found evidence for a compound in the superfusion fluid supplemented with iodoacetate that may be a reaction product of glutamate and iodoacetate. In some preparations superfusion with glucose‐free solutions caused a slowly developing increase in transparency and release of glutamate; in others the increase in transparency was more sudden and there was a larger release of glutamate. Seemingly, interference with the tissue metabolism can cause an uptake of extracellular material either by arrest of the Na+ pump or by the release of glutamate, depending on the conditions of the experiment.
THE BIOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF 6‐AMINODOPAMINE: SIMILARITY WITH 6‐HYDROXYDOPAMINE
Authors: Heikkila R. E. , Mytilineou Catherine , Cote L. J. , Cohen G. 
Published: October 2006

Abstract6‐aminodopamine was injected intraperitoneally into male Swiss–Webster mice. At 72 h post injection 6‐aminodopamine had caused a reduction in the endogenous content of heart norepinephrine, a decrease in the capacity of heart slices to accumulate [3H]‐norepinephrine in vitro, and a virtual disappearance of the adrenergic plexus of the mouse iris as viewed by fluorescence histochemistry. Similar data were obtained with the same dose of 6‐hydroxydopamine. These data suggest that 6‐aminodopamine causes a destruction of sympathetic nerve terminals. Model experiments showed that 6‐aminodopamine, like 6‐hydroxydopamine, generated H2o2both in vitro and in vivo. 6‐Aminodopamine, like 6‐hydroxydopamine, also blocked the accumulation of [3H]dopamine into slices of rat brain in vitro.
6‐AMINODOPAMINE‐INDUCED DEGENERATION OF CATECHOLAMINE NEURONS
Authors: Jonsson Gosta , Sachs Charlotte 
Published: October 2006

Abstractthe effects of 6‐aminodopamine on central and peripheral catecholamine neurons using fluorescence histochemical and isotope techniques have been investigated. Systematic administration of 6‐aminodopamine (20 mg/kg intraveneously) produced a rapid (within 1 h) and long‐lasting depletion of endogenous noradrenaline in adrenergic nerves of mouse atrium and iris with a concomitant loss of [3H]noradrenaline uptake. The effects were dosedependent. Accumulations of noradrenaline in non‐terminal axons were observed histochemically, indicating that 6‐aminodopamine induces neuronal damage. Desipramine completely blocked the 6‐aminodopamine induced noradrenaline depletion and reduction in [3H]noradrenaline uptake, indicating that 6‐aminodopamine has to be taken up by the axonal ‘membrane pump’ to produce its effects. Themonoamine oxidase inhibitor, nialamide, potentiated the effect of 6‐aminodopamine on [3H]noradrenaline uptake. 6‐Aminodopamine did not affect the cell bodies of the adrenergic neurons and there was a reappearance of adrenergic nerves and recovery of [3H]noradrenaline uptake. 6‐Aminodopamine does not seem to pass the blood‐brain barrier after systemic injection.Intraventricular injection of 6‐aminodopamine in rats led to a considerable reduction in endogenous whole brain noradrenaline and [3H]noradrenaline uptake in slices from cerebral cortex and hypothalamus. Similar, but less pronounced effects were observed on dopamine neurons in the caudate nucleus. Histochemically, pronounced accumulations of transmitter were observed in the axons of the catecholamine neurons. The results obtained favour the view that 6‐aminodopamine is able to produce an acute and selective degeneration of catecholamine neurons similar to that seen after the neurotoxicagent, 6‐hydroxydopamine. Both compounds seemed to be approximately equally potent in their neurotoxicity, although 6‐aminodopamine seemed to be more generally toxic.
NEUROCHEMISTRY OF THE SPINAL CORD IN BRITISH SADDLEBACK PIGLETS AFFECTED WITH CONGENITAL TREMOR, TYPE A‐IV, A SECOND FORM OF HEREDITARY CEREBROSPINAL HYPOMYELINOGENESIS
Authors: Patterson D. S. P. , Sweasey D. , Brush Pamela J. , Harding J. D. J. 
Published: October 2006

AbstractCongenital tremor, type A‐IV is an inherited abnormality of British Saddleback piglets characterized by the presence of poorly myelinated axons throughout the CNS. This is reflected by a general lowering of the spinal cord lipid content to about half control values. In particular, cerebroside and plasmalogen levels are markedly reduced.Changes in the fatty acid composition of total lipid extracts and two isolated cerebroside fractions suggest that there is a metabolic defect in which fatty acid chain elongation, desaturation and hydroxylation are sub‐optimal.Cholesterol esters accumulate, make up about 30 per cent of total sterols and contain more than 90 per cent of C16 and C18 fatty acids. These may have arisen through the breakdown of cerebrosides containing abnormal proportions of these acids. Slightly increased levels of acid hydrolase activity appear to confirm that abnormal or immature myelin is disposed of by enhanced macrophagic activity.Differences between this and type A‐III, the sex‐linked inherited form of cerebrospinal hypomyelinogenesis are discussed and comparisons made with two forms of murine leuko‐dystrophy.
GAS CHROMATOGRAPHIC ESTIMATION OF ACETYLCHOLINE IN THE RABBIT HEART USING A NITROGEN SELECTIVE DETECTOR
Authors: Kilbinger H. 
Published: October 2006

AbstractThe distribution of ACh in the rabbit heart was investigated by a modified gas chromatographic estimation method. ACh was extracted with perchloric acid, precipitated as reineckate and demethylated with sodium benzenethiolate. The tertiary amines derived from ACh and other choline esters were concentrated by a microdistillation procedure. Gas chromatography was performed using a nitrogen selective detector. In the range of concentrations between 0.4 and 2.5 nmol ACh per tissue sample the coefficient of variation was 5.2 per cent. The recovery of ACh added to heart extracts was 101 per cent. Evidence for the identity of the choline ester isolated from rabbit hearts and authentic ACh was obtained by equal retention times and by correspondence of the ratio N/C of the respective tertiary amines. Parallel measurements using gas chromatography and bioassay on the rat blood pressure yielded closely corresponding values of ACh levels in the rabbit heart. The concentration of ACh was much higher in the atria than in the ventricles. In both atria, and ventricles the ACh concentration was higher in the right than in the left part of the rabbit heart. Endogenous propionylcholine or butyrylcholine were not detected.