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  • 1
    Electronic Resource
    Electronic Resource
    N-Methyl-d-Aspartate-Sensitive Glutamate Receptors Induce Calcium-Mediated Arachidonic Acid Release in Primary Cultures of Cerebellar Granule Cells (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In primary cultures of cerebellar granule cells, glutamate, aspartate, and N-methyl-d-aspartate (NMDA) induced a dose-dependent release of [3H]arachidonic acid ([3H]AA) which was selective for these agonists and was inhibited by NMDA receptor antagonists. The agonist-induced [3H]AA release was reduced by quinacrine at concentrations that inhibited phospholipase A2 (PLA2) but affected neither the activity of phospholipase C (PLC) nor the hydrolysis of phosphoinositides induced by glutamate or quisqualate. Thus, the increased formation of AA was due to the receptor-mediated activation of PLA2 rather than to the action of PLC followed by diacylglycerol lipase. The receptor-mediated [3H]AA release was dependent on the presence of extracellular Ca2+ and was mimicked by the Ca2+ ionophore ionomycin. Pretreatment of granule cells with either pertussis or cholera toxin failed to inhibit the receptor-mediated [3H]AA release. Hence, in cerebellar granule cells, the stimulation of NMDA-sensitive glutamate receptors leads to the activation of PLA2 that is mediated by Ca2+ ions entering through the cationic channels functioning as effectors of NMDA receptors. A coupling through a toxin-sensitive GTP-binding protein can be excluded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1990.tb05771.x
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  • 2
    Electronic Resource
    Electronic Resource
    THE CEREBELLAR GLOMERULUS: ISOLATION AND METABOLIC PROPERTIES OF A PURIFIED FRACTION (1976)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 27 (1976), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— A method is described for large scale isolation of glomerular complexes from rabbit cerebellum. The purity of the fraction is 90–95%, measured by quantitative electron microscopy. In addition biochemical markers indicate a high degree of particle integrity. The glomeruli occur as mechanically separable units at 20–40 days of animal age and the amount of protein per particle is 15–20 × 10−11 g. The glomeruli accumulate [3H]GABA, and exhibit both high (Km 15μM) and low (Km 0.5 mM) affinity uptake properties. Glomeruli oxidize α-glycerophosphate and succinate particularly well, while glutamate, pyruvate and α-ketoglutarate are less effective as respiratory substrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1976.tb01574.x
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  • 3
    Electronic Resource
    Electronic Resource
    CALCIUM METABOLISM IN ISOLATED BRAIN CELLS AND SUBCELLULAR FRACTIONS (1974)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 22 (1974), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The accumulation of calcium ions by brain mitochondria and microsomes and by fractions containing neuronal or glial cells has been studied in vitro with techniques involving 45Ca and ultramicro-flame photometry. ATP and substrate-supported calcium accumulation by brain mitochondria was of the same magnitude as for mitochondria from other organs. Brain microsomes accumulated calcium approximately 15 times less than brain mitochondria. Variations in Na+/K+ ratios and in ATP/ADP ratios had a more marked influence on microsomal uptake than on mitochondrial uptake. The passive Ca2+ binding by glial cells was higher than neuronal perikarya and synaptosomes. Also the calcium accumulation ability in cell suspensions was slightly higher for glial cells as compared to neuronal perikarya. The calcium uptake by glial cells was stimulated by high external K+ concentration, which also was the case for nerve endings. The uptake in neuronal perikarya was unaffected by variations in K+ concentration. A comparison between neuronal and glial mitochondria showed that both reach a steady state level of similar magnitude, but that the rate of initial accumulation was greater for glial mitochondria. A high glial calcium accumulation was also observed for the microsomal fraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1974.tb12176.x
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  • 4
    Electronic Resource
    Electronic Resource
    CALCIUM FLUXES IN CULTURED AND BULK ISOLATED NEURONAL AND GLIAL CELLS (1977)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 29 (1977), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The influx and efflux of 45Ca has been studied in cultured human glioma and mouse neuroblastoma cells and in isolated fractions enriched in synaptosomes, neuronal and astrocytic perikarya from rabbit brain.The uptake of 45Ca was somewhat more efficient in glioma compared to neuroblastoma cells, whereas there was little difference in the rate of 45Ca uptake by isolated glial cells and neuronal perikarya. Isolated synaptosomes showed the highest rate of 45Ca accumulation. An increase of K concentration to 50 mm in the medium, with a corresponding lowering of Na, stimulated both glioma and glial as well as synaptosomal 45Ca uptake more markedly than the uptake by neuroblastoma cells and neuronal perikarya. Lowering the Na concentration and replacing it by choline had no effect on the cultured cells and astrocytes. Na-free media caused massive stimulation of 45Ca influx in all fractions and cells tested.The efflux of 45Ca was studied after preloading of cells. Three phases could be resolved from the desaturation curves. All cells had nearly similar half-lives for 45Ca efflux under standard conditions. Pulses of media containing 50 mm-K stimulated 45Ca efflux from glioma cells and astrocytes more efficiently than from neuroblastoma cells, neuronal perikarya and synaptosomes. The stimulated release was exclusively seen in Ca-containing media in experiments with the cultured cells and in Ca-free media in experiments with cell perikarya. The effect of transmitter pulses on the release of 45Ca was examined in a limited series. Acetylcholine and isoproterenol were found to stimulate 45Ca release more actively from glia than from neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1977.tb10698.x
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  • 5
    Electronic Resource
    Electronic Resource
    Group I metabotropic glutamate receptors participate in homocysteine-evoked neurotoxicity (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Homocysteine (HCY) neurotoxicity is known to be mediated by disturbances in methylation processes and by the NMDA receptor-mediated excitotoxicity. In this study we examined the role of group I metabotropic glutamate receptors (mGlyRs) in HCY-induced toxicity in cultured rat cerebellar granule neurons exhibited for 30 min, or cultured in the presence of HCY for 3 days. Acute neurodegeneration induced by 〉10 mm D,L-HCY, or subchronic damage evoked by 75–500 µm HCY were enhanced by 50 µm glycine and moderately inhibited by 0.5 µm MK-801, revealing the NMDA receptor-mediated portion of HCY neurotoxicity. Also group I mGluRs antagonists 25 µm LY367385 or MPEP given alone only moderately inhibited acute and subchronic HCY neurotoxicity, but given together with MK-801 completely prevented neurotoxicity. These results demonstrate that acute homocysteine-induced neurotoxicity is mediated cooperatively by group I mGluRs and NMDA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.15_7.x
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  • 6
    Electronic Resource
    Electronic Resource
    Mechanisms of dantrolene-induced neuroprotection against excitotoxic injury (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Dantrolene – an inhibitor of ryanodine receptors and calcium stabilizer – prevents ischemia- and excitotoxicity-evoked neurodegeneration. To elucidate the mechanisms of this phenomenon, we investigated effects of dantrolene on the NMDA- and glutamate-induced lesion and stimulation of 45Ca uptake in primary cultures of rat cerebellar granule neurons. Neurodegeneration was evaluated after 24 h with the propidium iodide staining. Bcl-2 immunoreactivity in cell homogenates was measured by immunoblotting. The results demonstrated that dantrolene applied at micromolar concentrations inhibits in a dose-dependent manner NMDA- and glutamate-evoked 45Ca uptake in neurones and induces neuroprotection. This effect was additive to known effects of DMSO, a vehicle to dantrolene. Dantrolene failed to induce changes in Bcl-2 immunoreactivity. Thus, dantrolene-induced neuroprotection against excitotoxicity may be at least partially mediated by its inhibitory effect on the NMDA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.16_5.x
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  • 7
    Electronic Resource
    Electronic Resource
    GlycineB antagonists as potential therapeutic agents (1998)
    Springer
    Amino acids 14 (1998), S. 235-239 
    Details
    ISSN: 1438-2199
    Keywords: NMDA receptors ; Glutamate ; Behaviour ; MRZ 2/570 ; MRZ 2/576 ; L-701,324
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is not clear what therapeutic application is most likely for agents blocking glycine site of the NMDA receptors (glycineB). Majority of the studies to date used either glycineB antagonists with doubtful brain penetration or partial agonists. Following systemic administration to rats of our newly developed glycmeB antagonists (MRZ 2/570; 2/571 and 2/576) and L-701,324 (MSD) as a reference agent the following behavioural effects were observed: weak (if any) antiparkinsonian-like effects, lack of anxiolytic activity, inhibition of physical and motivational aspects of morphine dependence and neuroprotective activity in global ischaemia. The side effects include: sedation, ataxia, and myorelaxation. We detected neither vacuolisation in the cingulate cortex nor impairment of pre-pulse inhibition indicating lack of psychotomimetic potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345268
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  • 8
    Electronic Resource
    Electronic Resource
    Protection against post-ischaemic neuronal loss in gerbil hippocampal CA1 by glycine b and AMPA antagonists (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 1249-1254 
    Details
    ISSN: 1435-1463
    Keywords: Forebrain ischaemia ; gerbil ; glycine b antagonists ; MRZ 2/570 ; MRZ 2/576 ; NBQX ; hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Novel antagonists of the glycineB site of the NMDA receptor (MRZ 2/570, MRZ 2/576), and an AMPA receptor antagonist, NBQX were tested in 3-min. global ischaemia in gerbils. Untreated animals showed after 14 days a loss of almost 90% of pyramidal neurones in the CA1 region, which was prevented by NBQX, and reduced to 50% by both glycineB antagonists. NBQX produced a delayed, long lasting (up to 24 hr) hypothermia while hypothermia with both glycineB antagonists was transient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01294724
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of in vitro anoxia on calcium metabolism in the cerebral cortex (1988)
    Springer
    Bulletin of experimental biology and medicine 105 (1988), S. 301-304 
    Details
    ISSN: 1573-8221
    Keywords: anoxia ; mitochondria ; microsomes ; synaptosomes ; membrane-bound Ca++
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00835733
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  • 10
    Electronic Resource
    Electronic Resource
    Metabolic disturbances of synaptosomes isolated from ischemic gerbil brain (1985)
    Springer
    Neurochemical research 10 (1985), S. 649-665 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cerebral ischemia, induced for 10 min by bilateral common carotid ligation in the Mongolian gerbil, on the brain and synaptosomal content of phospholipids and free fatty acids were measured. Moreover, the incorporation of arachidonic acid and oleoyl-CoA into phospholipids, as well as the respiration and the accumulation of45Ca, norepinephrine, dopamine, choline, glutamate, and γ-aminobutyrate in the ischemic brain synaptosomal fraction were studied. Analyses of lipids showed a drop in phospholipids content with concomitant increase of lysocompounds and free fatty acids in ischemic cerebral cortex. Disturbances in lipid metabolism including rapid phospholipids hydrolysis and changes in the incorporation of arachidonic acid into inositol and choline phosphoglycerides were also shown in the synaptosomal fraction of ischemic brain. The uptake of neurotransmitter substances, expressed as a percent of control value, was reduced 21% for norepinephrine, 40% for dopamine, 20% for choline, 24% for glutamate and 13% for γ-aminobutyrate in ischemic synaptosomes. There was no significant effect of ischemia on synaptosomal respiration and45Ca uptake in both control and high potassium media. the inhibition of neurotransmitter uptake in ischemic brain synaptosomes may be caused by the disturbance of fatty acid metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00964404
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