High Sensitivity of Glutamate Uptake to Extracellular Free Arachidonic Acid Levels in Rat Cortical Synaptosomes and Astrocytes

Abstract: By using both synaptosomes and cultured astrocytes from rat cerebral cortex, we have investigated the inhibitory action of arachidonic acid on the high‐affinity glutamate uptake systems, focusing on the possible physiological significance of this mechanism. Application of arachidonic acid (1–100 μM) to either preparation leads to fast (within 30 s) and largely reversible reduction in the uptake rate. When either melittin (0.2–1 mg/ml), a phospholipase A2 activator, or thimerosal (50–200 μM), which inhibits fatty acid reacylation in phospholipids, is applied to astrocytes, both an enhancement in extracellular free arachidonate and a reduction in glutamate uptake are seen. The two effects display similar dose dependency and time course. In particular, 10% uptake inhibition correlates with 30% elevation in free arachidonate. whereas inhibition ≥60% is paralleled by threefold stimulation of arachidonate release. In the presence of albumin (1–10 mg/ml), a free fatty acid‐binding protein, inhibition by either melittin, thimerosal, or arachidonic acid is prevented and an enhancement of glutamate uptake above the control levels is observed. Our data show that neuronal and glial glutamate transport systems are highly sensitive to changes in extracellular free arachidonate levels and suggest that uptake inhibition may be a relevant mechanism in the action of arachidonic acid at glutamatergic synapses.

[1]  A. Volterra,et al.  A particle beam-liquid chromatography-mass spectrometry method for the determination of lipoxygenase metabolites of arachidonic acid. , 1992, Analytical biochemistry.

[2]  M. Miras-Portugal,et al.  Inhibition of Glutamate Release by Arachidonic Acid in Rat Cerebrocortical Synaptosomes , 1991, Journal of neurochemistry.

[3]  E. Costa,et al.  N‐Methyl‐d‐Aspartate‐Sensitive Glutamate Receptors Induce Calcium‐Mediated Arachidonic Acid Release in Primary Cultures of Cerebellar Granule Cells , 1990, Journal of neurochemistry.

[4]  D. Attwell,et al.  The release and uptake of excitatory amino acids. , 1990, Trends in pharmacological sciences.

[5]  J. Bockaert,et al.  Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors , 1990, Nature.

[6]  C. Sanfeliu,et al.  Exposure toN-methyl-d-aspartate increases release of arachidonic acid in primary cultures of rat hippocampal neurons and not in astrocytes , 1990, Brain Research.

[7]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[8]  M. Lynch,et al.  Arachidonic Acid Increases Inositol Phospholipid Metabolism and Glutamate Release in Synaptosomes Prepared from Hippocampal Tissue , 1990, Journal of neurochemistry.

[9]  R. Massarelli,et al.  5α-Reductase activity in isolated and cultured neuronal and glial cells of the rat , 1990, Brain Research.

[10]  S. Franks,et al.  Uptake, distribution and release of 3H-arachidonic acid from human endometrium. , 1990, Prostaglandins, Leukotrienes and Essential Fatty Acids.

[11]  T. Bliss,et al.  Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: An in vivo study in the dentate gyrus of the rat , 1989, Neuroscience.

[12]  D. Attwell,et al.  Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells , 1989, Nature.

[13]  T. Bliss,et al.  Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus , 1989, Nature.

[14]  C. Agardh,et al.  Arachidonic Acid Metabolism in Seizures , 1989, Annals of the New York Academy of Sciences.

[15]  D. Okada,et al.  Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses , 1989, Neuroscience Letters.

[16]  J. Bockaert,et al.  NMDA receptors activate the arachidonic acid cascade system in striatal neurons , 1988, Nature.

[17]  E. Costa,et al.  Activation of N-methyl-D-aspartate-sensitive glutamate receptors stimulates arachidonic acid release in primary cultures of cerebellar granule cells , 1988, Neuropharmacology.

[18]  T. Bliss,et al.  Induction but not maintenance of calcium-induced long-term potentiation in dentate gyrus and area CA1 of the hippocampal slice is blocked by nordihydroguaiaretic acid , 1988, Neuroscience Letters.

[19]  R. Jackisch,et al.  Prostanoid formation in primary astroglial cell cultures: Ca2+-dependency and stimulation by A 23187, melittin and phospholipases A2 and C , 1987, Neurochemistry International.

[20]  M. Johnston,et al.  Perinatal Hypoxia‐Ischemia Disrupts Striatal High‐Affinity [3H]Glutamate Uptake into Synaptosomes , 1986, Journal of neurochemistry.

[21]  A. Yu,et al.  Effects of Arachidonic Acid on Glutamate and γ‐Aminobutyric Acid Uptake in Primary Cultures of Rat Cerebral Cortical Astrocytes and Neurons , 1986, Journal of neurochemistry.

[22]  S. Lin-Shiau,et al.  Mode of inhibitory action of melittin on Na+-K+-ATPase activity of the rat synaptic membrane. , 1985, Biochemical pharmacology.

[23]  P. Roberts,et al.  Neurotoxicity of L‐Glutamate and DL‐Threo‐3‐Hydroxyaspartate in the Rat Striatum , 1985, Journal of neurochemistry.

[24]  H. Benveniste,et al.  Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral Microdialysis , 1984, Journal of neurochemistry.

[25]  R. Ockner,et al.  Modulation of membrane transport by free fatty acids: inhibition of synaptosomal sodium-dependent amino acid uptake. , 1983, Biochemistry.

[26]  P. Chan,et al.  Reductions of Γ‐Aminobutyric Acid and Glutamate Uptake and (Na++ K+)‐ATPase Activity in Brain Slices and Synaptosomes by Arachidonic Acid , 1983, Journal of neurochemistry.

[27]  R. Klausner,et al.  LIPID DOMAINS IN MEMBRANES * , 1982, Annals of the New York Academy of Sciences.

[28]  D. Rhoads,et al.  Effects of Free Fatty Acids on Synaptosomal Amino Acid Uptake Systems , 1982, Journal of neurochemistry.

[29]  R. Irvine.  How is the level of free arachidonic acid controlled in mammalian cells? , 1982, The Biochemical journal.

[30]  S. Rehncrona,et al.  Brain Cortical Fatty Acids and Phospholipids During and Following Complete and Severe Incomplete Ischemia , 1982, Journal of neurochemistry.

[31]  U Kragh-Hansen,et al.  Molecular aspects of ligand binding to serum albumin. , 1981, Pharmacological reviews.

[32]  K. McCarthy,et al.  Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue , 1980, The Journal of cell biology.

[33]  R. Klausner,et al.  Lipid domains in membranes. Evidence derived from structural perturbations induced by free fatty acids and lifetime heterogeneity analysis. , 1980, The Journal of biological chemistry.

[34]  N. Bazan,et al.  Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. , 1970, Biochimica et biophysica acta.

[35]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[36]  A. Volterra,et al.  A role for the arachidonic acid cascade in fast synaptic modulation: ion channels and transmitter uptake systems as target proteins. , 1992, Advances in experimental medicine and biology.

[37]  W. Shier.  Activation of high levels of endogenous phospholipase A2 in cultured cells. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[38]  V. P. Whittaker,et al.  The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. , 1962, Journal of anatomy.