bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEVELOPMENTAL CHANGES IN THE KINETICS OF γ‐AMINOBUTYRIC ACID TRANSPORT BY CHICK RETINA
Authors: Tunnicliff G. , Firneisz G. , Ngo T. T. , Martin R. O. 
Published: October 2006

Abstract—Isolated retinas from chick embryos and mature animals were incubated in [3H]GABA at 25°C for 10 min in order to investigate kinetic properties of the amino acid uptake system. Embryo retina accumulated [3H]GABA by two distinct kinetic systems with Km values of the order 10−4m and 10−5m for the low‐ and high‐affinity mechanisms respectively. However, as the retina matured, the high‐affinity process disappeared and only the low‐affinity system was detectable. No obvious explanation can be offered for this phenomenon although a similar observation has previously been made in chick brain by other workers.
DISTRIBUTION OF CHOLINE ACETYLTRANSFERASE AND GLUTAMATE DECARBOXYLASE WITHIN THE SUBSTANTIA NIGRA AND IN OTHER BRAIN REGIONS FROM CONTROL AND PARKINSONIAN PATIENTS
Authors: Lloyd K. G. , Möhler H. , Heitz Ph. , Bartholini G. 
Published: October 2006

Abstract—The distribution of choline acetyltransferase (ChAc, EC 2.3.1.6) and l‐glutamate 1‐carboxylyase (glutamate decarboxylase, GAD, EC 4.1.1.15) was studied in serial frontal slices of the substantia nigra (SN) (pars compacta, PC; pars reticulata, PR; an intermediate region, IR) as well as in other brain areas from post mortem tissue of control and Parkinsonian patients.Within the SN from control brain ChAc and GAD activities showed a distinctive distribution: ChAc activity in PC was higher than in PR and IR by 427% and 253% respectively and within PC the enzyme activity in the rostral part exceeded that in the control part by 353%. The GAD activity in PC was higher by 41% than that in PR and within PC seemed to be higher in the caudal than in the rostral part. For both enzyme activities there were no significant differences between PR and IR or within these regions.In Parkinsonian brain both ChAc and GAD activities were reduced to 15‐25% of controls in all 3 regions of the SN. The distinctive distribution of ChAc and GAD activity found in the SN of control brain was abolished: no difference was observed between the 3 regions. However, within PC the ChAc activity was lower in the medial than in the rostral part.Since nigral ChAc is possibly located in interneurons, the decrease in enzyme activity may be connected with the cell loss observed in the SN of Parkinsonian brain.By contrast, nigral GAD is probably contained in terminals of strio‐nigral neurons and the decrease in enzyme activity in Parkinson's disease in the absence of striatal cell loss, may reflect a change in the functional state of these GABA neurons.Among various areas of control brains ChAc activity was highest in caudate nucleus and putamen while GAD was highest in SN. caudate nucleus, putamen and cerebral cortex. In Parkinsonian brain the most severe reduction in ChAc and GAD activities was found in the SN.
EFFECTS OF INGESTION OF A CARBOHYDRATE‐FAT MEAL ON THE LEVELS AND SYNTHESIS OF 5‐HYDROXYINDOLES IN VARIOUS REGIONS OF THE RAT CENTRAL NERVOUS SYSTEM
Authors: Colmenares J. L. , Wurtman R. J. , Fernstrom J. D. 
Published: October 2006

Abstract—The concentrations of tryptophan, serotonin (5‐HT), and 5‐hydroxyindoleacetic acid (5‐HIAA) in spinal cord and most brain regions increase 2 h after fasted rats begin to consume a carbohydrate‐fat meal: indole levels rise in all portions of the brain studied, but the increase is not statistically significant in the hypothalamus and corpus striatum. The rate at which the brain synthesizes 5‐hydroxy‐indoles (as estimated in vivo by measuring 5‐hydroxytryptophan accumulation following an injection of the decarboxylase inhibitor RO4‐4602) is also accelerated in all of the regions in which the experimental diet elevates tryptophan, 5‐HT and 5‐HIAA levels. These observations indicate that the previously reported increase in brain 5‐hydroxyindole levels following consumption of a protein‐free meal reflects accelerated serotonin synthesis, and occurs within both the cell bodies and the terminals of serotonin‐containing neurons. It is possible that diet‐induced changes in neuronal serotonin levels influence the quantities of the neurotransmitter released into synapses, either spontaneously or in response to drugs.
BRAIN UPTAKE AND PROTEIN INCORPORATION OF AMINO ACIDS STUDIED IN RATS SUBJECTED TO PROLONGED HYPERPHENYLALANINAEMIA
Authors: Antonas K. N. , Coulson W. F. 
Published: October 2006

Abstract— The uptake into brain and the incorporation into brain protein of intraperitoncally administered, labelled amino acids has been studied in myelinating rats during prolonged hyperphenylalaninaemia maintained by administration of p‐chlorophenylalanine. Compared with controls, there was a 50% reduction in both uptake and incorporation into protein of leucine and a parallel reduction in the acid‐soluble leucine pool. With glycine and lysine no such changes were observed. On the other hand, when each of the three amino acids was injected directly into the brain, the only significant differences observed between controls and hyperphenylalaninaemic animals were again with leucine, which showed an increased incorporation into protein and an increased specific activity in the otherwise reduced acid‐soluble pool.It is concluded that hyperphenylalaninaemia reduces the rate of transport of leucine into the brain and hence reduces the brain pool of leucine, but that any effects on protein synthesis are small. The validity of the model, and the implications of the findings, in relation to phenylketonuria, are discussed.
REGIONAL AND SUBCELLULAR DISTRIBUTION AND KINETIC PROPERTIES OF RAT BRAIN CHOLINE ACETYLTRANSFERASE–SOME FUNCTIONAL CONSIDERATIONS
Authors: Kuczenski R. , Segal D. S. , Mandell A. J. 
Published: October 2006

Abstract—The kinetic properties of soluble and membrane‐bound choline acetyltransferase (ChAc) were determined as a function of homogenization media and solubilization procedure in various regions of rat brain. Treatment of homogenate and/or subcellular fractions with KCl, Triton X‐100, or ether dramatically altered the apparent Vmax and the degree of solubilization of the enzyme, but no fraction exhibited Km values substantially different from 12 μM for acetyl‐CoA and 200 μM for choline. On the other hand, increasing the ionic strength of the assay medium for a given fraction from 0‐02 M to 0‐5 M increased both Vmax and Km values for both substrates. The absolute levels and subcellular distribution of ChAc were determined in 11 brain regions to localize cholinergic cell bodies and nerve endings. Levels of ChAc varied from 139 m‐units/g tissue in caudate‐putamen to 5‐7 m‐units/g tissue in cerebellum. The fraction of ChAc activity associated with synaptosomes varied from near 75 per cent in caudate‐putamen, hippocampus and cortical regions to near 20 per cent in septum, locus coeruleus area and substantia nigra area. The apparent parallel distribution of cholinergic and catecholaminergic nerve endings is discussed in terms of a hypothetical model for the pathophysiology and treatment of Parkinson's syndrome.
MOBILIZATION OF SYNAPTIC MEMBRANE‐BOUND CALCIUM BY ACIDIC AMINO ACIDS1
Authors: Tan A. T. 
Published: October 2006

Abstract—A fluorescent chelate probe (chlorotetracycline) and radioactive 45Ca were used to study the effects of amino acids on the calcium bound to external synaptosomal membranes isolated from guineapig brain. Acidic amino acids released some of the membrane‐bound calcium. On the basis of 45Ca studies, the order of mobilization potency‐DL‐homocysteic acid and l‐cysteic acid > l‐aspartic acid, l‐glutamic acid, d‐glutamic acid > N‐methyl‐dl‐glutamic acid and dl‐cyteic acid‐is in general agreement with that found by fluorescent chelate method with the exception of N‐methyl‐dl‐aspartic acid and N‐methyl‐dl‐glutamic acid, which are at least as potent as dl‐homocysteic acid. This order of potency is observed only with a fraction enriched in external synaptosomal membranes, but not with microsomes, myelin and mitochondria. Neutral and basic amino acids, including glutamine. glycine and γ‐aminobutyric acid are ineffective. These results suggest that acidic amino acids have a specific ability to mobilize membranebound calcium; this is consistent with the proposed role of some of these compounds as excitatory transmitters in the central nervous system.
ALTERATIONS IN BRAIN RNA METABOLISM FOLLOWING CHRONIC ETHANOL INGESTION
Authors: Tewari S. , Fleming E. W. , Noble E. P. 
Published: October 2006

Abstract—The in vivo labelling of various brain RNA fractions was found to be altered due to chronic ethanol ingestion by C57BL/6J mice. Ingestion of ethanol resulted in a marked decrease in the incorporation of intraventricularly injected [5‐3H] orotic acid into tRNA, rRNA and polyribosomal RNA. The inhibition was more pronounced in the polyribosomal fraction than the ribosomal fraction. In the nucleus, a biphasic effect of ethanol was demonstrated in the nRNA fraction where increased incorporation of precursor label at early time points was followed by marked depression. Absence of a similar increase in the cytoplasmic RNA fractions is suggestive of a possible defect in the transport of RNA from nucleus to cytoplasm resulting in the accumulation of RNA in the nucleus. Ethanol ingestion had no effect on the synthesis of acid soluble nucleotides following the in vivo administration of [5‐3H]orotic acid or [5‐3H]uridine into the brain. Over 90 per cent of the radioactivity in either ‘control’ or ‘ethanol’ brain could be recovered in the UMP fraction with negligible conversion to GMP, AMP or CMP. The results suggest that the observed changes in RNA metabolism following chronic ethanol ingestion are due to an alteration in the transcription and/or the processing of RNA in the nucleus rather than a function of reduced availability of nucleotides.
THE EFFECTS OF HYPERKETONEMIA ON GLUTAMATE AND GLUTAMINE METABOLISM IN DEVELOPING RAT BRAIN
Authors: Ozand P. T. , Stevenson J. H. , Tildon J. T. , Cornblath M. 
Published: October 2006

Abstract— The effect of increased exposure to ketone bodies in the developing rat brain suggest that intrauterine and postnatal hyperketonemia lead to an altered metabolism of glutamine and glutamate. It is postulated that this effect is related to the delayed development of glutaminase (l‐glutamine amido‐hydrolase EC 3.5.1.2) and glutamate dehydrogenase (l‐glutamate: NAD oxidoreductase EC 1.4.1.2).The specific activities of glutamate dehydrogenase (GDH), glutaminase and glutamine synthetase (l‐glutamate: ammonia ligase EC 6.3.1.2) in the brains of newborn rats increased during early development. A positive correlation was observed between the specific activity of glutaminase and the concentration of glutamate in the brain as well as between the concentrations of blood and brain glutamine and glutamate in both control and hyperketonemic pups. This indicates a different degree of permeability and metabolism for glutamine and glutamate in the brain during the neonatal period, as compared to adulthood.In hyperketonemic pups, glutamine and glutamate metabolism were found to differ from that in control animals. The concentrations of glutamate were higher, and glutamine lower, in both the blood and brain as compared to that in controls. The concentrations of α‐ketoglutarate were also lower in their brain. In the brains of hyperketonemic and control pups, the concentration of malate was the same. During the first 3 weeks of life the increase of spec. act. of GDH and glutaminase was found to be suppressed in the brains of hyperketonemic pups. However, the spec. act. of glutamine synthetase was similar to that of the control pups.
METABOLISM OF BIOGENIC AMINES IN NEUROBLASTOMA AND GLIOMA CELLS IN CULTURE1
Authors: Skaper S. D. , Adelson G. L. , Seegmiller J. E. 
Published: October 2006

Abstract—The kinetic parameters of monoamine oxidase (MAO; E.C 1.4.3.4) and catechol‐O‐methyl‐transferase (COMT; EC 2.1.1.6) were evaluated in extracts of adrenergic and non‐adrenergic mouse neuroblastoma cells and in rat glioma cells. Using the naturally‐occurring substrates tyramine, tryptamine, serotonin and norepinephrine, the affinity of MAO for a given substrate was independent of the presence of the catecholaminergic pathway or cell type used, with apparent Km values ranging from 8–14 μM for tryptamine to 510–580 μM for norepinephrine. The MAO activity in glioma cells was substantially greater than in either neuroblastoma clone, but Vmax values varied little with substrate among cell lines. Both the neuronal and glial COMT had a similar Km for I‐norepinephrine (200μM); the corresponding Vmax values were also similar among the different cell lines, but represented only 2–10% of the maximal MAO activity. Neuroblastoma and glioma cells, when grown from early logarithmic to stationary phase, showed no significant changes in specific activity of either MAO or COMT. Growth of cells for 3 days with 1 mM‐N6,O2′ ‐dibutyryl adenosine‐3′,5′‐cyclic monophosphate resulted in no marked change in either MAO or COMT activity.These results suggest that in neurons neither MAO nor COMT plays a major role in the type of transmitter inactivation that is analogous to that of acetylcholinesterase in cholinergic synapses. The occurrence of considerable MAO and acetylcholinesterase activities in glioma cells may indicate a role for these cells in neurotransmitter inactivation.
MOUSE BRAIN PROTEIN COMPOSITION DURING POSTNATAL DEVELOPMENT: AN ELECTROPHORETIC ANALYSIS
Authors: Kelly P. T. , Luttges M. W. 
Published: October 2006

Abstract—Changes in the concentrations of mouse brain proteins during postnatal maturation were characterized by a combination of subcellular fractionation and electrophoresis. Sodium dodecyl sulfate gel electrophoresis revealed changing protein concentrations in fractions enriched in nuclei, mitochondria plus synaptic endings, microsomes and cytosol. Postnatal maturational changes in protein concentrations were most pronounced in fractions of purified myelin membranes. The use of exponential gradient gels resulted in increased resolution of low molecular weight myelin proteins. Nuclei treated with Triton X‐100 exhibited no change in relative histone concentrations during brain maturation. Nonnuclear contamination of untreated nuclear fractions was shown to be a potential source of erroneous interpretations. These findings are discussed in terms of genetic products and sodium dodecyl sulfate polyacrylamide gel electrophoresis resolution.
ATP HYDROLASE ACTIVITY ASSOCIATED WITH MICROTUBULES REASSEMBLED FROM BOVINE SPLENIC NERVE–A CAUTIONARY TALE
Authors: Banks P. 
Published: October 2006

Abstract– ATP‐hydrolase activity is present in microtubules prepared from extracts of bovine splenic nerve.The reassembled microtubules contain several proteins in addition to tubulin, including two which appear to be similar to the ‘dynein‐like’ polypeptides found in preparations of brain microtubules by other authors.The sensitivity of the ATP‐hydrolase activity to Na+ and K+ ions and to ouabain suggests that it can be ascribed to a membrane‐bound sodium transport ATP‐hydrolase rather than to ‘dynein‐like’ polypeptides. This view is supported by the presence of phospholipids in the microtubule preparations even though membrane fragments could not be demonstrated by electron microscopy.
THE METABOLIC TURNOVER OF MOLECULAR SPECIES OF PHOSPHATIDYLINOSITOL and ITS PRECURSOR PHOSPHATIDIC ACID IN GUINEA‐PIG CEREBRAL HEMISPHERES
Authors: Luthra M. G. , Sheltawy A. 
Published: October 2006

Abstract– The molecular species composition of phosphatidylinositol from guinea‐pig cerebral hemispheres was studied and found similar to that of phosphatidylinositol from ox cerebral hemispheres. In both cases the tetraenoic species was predominant. Phosphatidic acid from guinea‐pig cerebral hemispheres contained two major molecular species; the monoenoic and hexaenoic (33.4 and 24 mol/100 mol respectively).In order to study the metabolism of molecular species of phosphatidic acid and phosphatidylinositol in the cerebral hemispheres, guinea‐pigs were injected intracisternally with 32Pi and [U‐14C]glucose. After 5 min of isotopic exchange, the specific radioactivity of 32P in phosphatidylinositol was nearly equal to that in phosphatidic acid, whereas specific radioactivity of 14C in the glycerol was 1.4 times and in the fatty acids nearly 0.5 times that in the phosphatidic acid respectively, indicating metabolic heterogeneity of both phospholipids.The glycerol specific radioactivity was different in all the molecular species of phosphatidic acid being greatest in the monoenoic and least in the tetranenoic species. When the molecular species were arranged in this way, the order was representative of their relative rates of synthesis by acylation of glycerol‐3‐phosphate. An almost opposite order was obtained when the molecular species were arranged according to their phosphate/glycerol radioactivity ratios, indicating the relative contribution of the diacylglycerol kinase pathway to their formation.When the specific radioactivity values and ratios of phosphatidylinositol were similarly considered, the orders of the molecular species were, on the whole, similar to that of phosphatidic acid. This indicated that synthesis de novo (Paulus & Kennedy, 1960) was operative in the formation of most of its molecular species, but due to other considerations it was concluded that part of the tetraenoic, and probably the whole of saturated phosphatidylinositol may be formed by transacylation reactions.The results are discussed in terms of the experimental limitations of previous and present techniques for the analysis of phospholipid molecular species.
PYRIMIDINE BIOSYNTHESIS AND ITS REGULATION IN THE DEVELOPING RAT BRAIN1
Authors: Tremblay G. C. , Jimenez U. , Crandall D. E. 
Published: October 2006

Abstract—Measurements of the incorporation of [14C]NaHCO3 into orotic acid, uridine nucleotides and RNA in tissue minces establish the occurrence of the complete orotate pathway for the de novo biosynthesis of pyrimidines in rat brain. Selective inhibition of the incorporation of various radiolabelled precursors into orotic acid by uridine demonstrates the operation of a feedback control mechanism in brain minces and indicates carbamoylphosphate synthetase to be the site of inhibition; purine nucleosides were similarly found to inhibit the de novo biosynthesis of pyrimidines.The activity of the orotate pathway, as assessed by the rate of incorporation of [14C]NaHCO3 into orotic acid, was found to be very high in fetal brain and to decline rapidly with neurological development; the mature rat brain exhibits less than 1% of the activity of the fetal brain at 18 days of gestation. Comparative studies on the ability of minces of the brain and several extraneural tissues to utilize [14C]NaHCO3 and [14C]aspartate as precursors of orotic acid lead us to speculate that variations in the ability of tissues to synthesize orotic acid de novo are determined by similar variations in their ability to synthesize carbamoylphosphate.
EFFECTS OF TRYPTOPHAN ON SEROTONIN IN NERVE ENDINGS1
Authors: McBride W. J. , Hyde T. P. , Smith, J. E. , Lane J. D. , Aprison M. H. 
Published: October 2006

Abstract—Preparations of crude synaptosome fractions (P2) from the telencephalon and from the diencephalon plus optic lobes of the pigeon and from the telencephalon of the rat were used to study the effects of l‐tryptophan on (a) the levels of serotonin (5‐HT), norepinephrinc (NE) and dopamine in nerve endings and (b) the release of radioactive 5‐HT, NE and dopamine from nerve endings. The level of 5‐HT was significantly higher (P < 0–05) in the P2 fraction isolated from the telencephalon of pigeons given intramuscular injections of 300mg/kg of l‐tryptophan in comparison to control values (1.11 ± 0.09 vs 0.74 ± 0.13 nmol/g original tissue wt). A smaller but not statistically significant increase in 5‐HT was noted in the P2 fractions isolated from the diencephalon plus optic lobes of pigeons given injections of l‐tryptophan. In vitro studies using preparations of synaptosomes (from both pigeon and rat) labelled with [3H]5–HT demonstrated that 1.0 mm‐l‐tryptophan caused a 30% increase (P < 0.05) in the release of [3H]5‐HT over control values. This effect by l‐tryptophan was blocked when a decarboxylase inhibitor was added to the medium. Tryptophan had no effect on the levels of NE or dopamine in these nerve endings nor did it have any effect on the release of these two amines from these preparations of synaptosomes. The results are discussed in terms of the role of serotonin in producing depression in pigeons working on a certain learned behavioural task.
OCTOPAMINE IN MAMMALIAN BRAIN: RAPID POST MORTEM INCREASE AND EFFECTS OF DRUGS
Authors: Harmar A. J. , Horn A. S. 
Published: October 2006

Abstract—A modified enzyme radiochemical assay for octopamine, based upon the N‐methylation of octopamine by the enzyme phenylethanolamine N‐methyl transferase (S‐Adenosyl‐1‐methionine: phenylcthanolamine N‐methyl transferase EC 2.1.28), has been developed. [3H]Methyl‐S‐adenosyl‐l‐ methionine was used as methyl donor, and the reaction products separated by thin‐layer chromatography prior to liquid scintillation counting. The method had a sensitivity of about 100 pg, and was suitable for the measurement of endogenous octopamine levels in mammalian brain. Although the method could be used for the determination of phenylethanolamine with similar sensitivity, concentrations of this amine in brain were too low for routine measurement. Octopamine levels in the brains of a number of mammalian species were determined using this procedure. Concentrations of the amine in mouse brain were lower in animals killed by rapid freczing than in animals killed by decapitation; a further increase in brain octopamine took place post‐mortem. Brain octopamine was increased following treatment with MAO inhibitors, p‐chlorophenylalanine, phenylalanine, tyrosine or phenylethylamine. The effects of tyrosine and phenylethylamine were greatly increased by pretreatment with a monoamine oxidase inhibitor. The antidepressants imipramine and iprindole gave rise to increased brain octopamine concentrations, possibly through an effect upon monoamine oxidase. Administration of chlordiazepoxide chlorpromazine, thyroxine, or reserpine had no effect upon brain octopamine.
A STUDY OF GLYCOLYTIC AND PENTOSE PHOSPHATE SHUNT ENZYMES IN RELATIONSHIP TO THE ALTERED PERMEABILITY IN THE BLOOD‐BRAIN BARRIER
Authors: Bennett M. J. , Ogilvy. K. M. , Blake G. M. , Lewtas N. , Timperley W. R. 
Published: October 2006

AbstractThe activities of a number of glycolytic and hexose‐monophosphate shunt cnzymes in 14 cases of intracranial pathology have been compared with specific uptake of the radioactive tracer 99m Tc‐pertechnetate. Strong positive correlations were observed betwcen isotope uptake and the activities of hexokinase and glucose‐6‐phosphate dehydrogenase. No close correlation was observed with other enzymes studied. Hexokinase is considered to be one of the major rate determining enzymes for the glycolytic catabolism of carbohydratcs and the subsequent production of nucleotidc triphophosphates which are vital in active transport mechanisms. This could indicate an important role for this enzyme in blood‐brain barrier kinetics.