Astrocyte Heterogeneity: Endogenous Amino Acid Levels and Release Evoked by Non‐<i>N</i>‐Methyl‐D‐Aspartate Receptor Agonists and by Potassium‐Induced Swelling in Type‐1 and Type‐2 Astrocytes

Levi, Giulio; Patrizio, Mario

doi:10.1111/j.1471-4159.1992.tb10073.x

Cited by 81 publications

(39 citation statements)

References 58 publications

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“…The levels of [D-serine] i found here are in accordance with concentrations found in previous studies for this amino acid (11) and also for other amino acids in astrocytes (34,35). By using a previously undescribed highly sensitive bioassay, we demonstrate that GluRsinduced D-serine release operates by means of a Ca 2ϩ -dependent and SNARE protein-dependent process.…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, the large fraction of D-serine present in the cytosol may represent a source for nonvesicular release through connexin hemichannels or volume anion channels, as reported for glutamate or ATP (21,34,41). A more widespread analysis of factors controlling D-serine compartmentalization in astrocytes and of the physiological stimuli controlling its release are necessary to define the conditions leading to its synaptic availability in the active brain.…”

Section: Discussionmentioning

confidence: 99%

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Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine

Mothet

Pollegioni

Ouanounou

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

400

350

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The gliotransmitter D-serine is released upon (S)-␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid͞kainate and metabotropic glutamate receptor stimulation, but the mechanisms involved are unknown. Here, by using a highly sensitive bioassay to continuously monitor extracellular D-serine levels, we have investigated the pathways used in its release. We reveal that D-serine release is inhibited by removal of extracellular calcium and augmented by increasing extracellular calcium or after treatment with the Ca 2؉ ionophore A23187. Furthermore, release of the amino acid is considerably reduced after depletion of thapsigargin-sensitive intracellular Ca 2؉ stores or chelation of intracellular Ca 2؉ with 1,2-bis(2-aminophenoxy)ethane-N,N,N ,N -tetraacetate-acetoxymethyl ester. Interestingly, D-serine release also was markedly reduced by concanamycin A, a vacuolar-type H ؉ -ATPase inhibitor, indicating a role for the vesicular proton gradient in the transmitter storage͞release. In addition, agonist-evoked D-serine release was sensitive to tetanus neurotoxin. Finally, immunocytochemical and sucrose density gradient analysis revealed that a large fraction of D-serine colocalized with synaptobrevin͞VAMP2, suggesting that it is stored in VAMP2-bearing vesicles. In summary, our study reveals the cellular mechanisms subserving D-serine release and highlights the importance of the glial cell exocytotic pathway in influencing CNS levels of extracellular D-serine.glia ͉ synaptobrevin ͉ D-amino acid ͉ vesicles ͉ tetanus neurotoxin A strocytes play pivotal roles in synaptic transmission by controlling transmitter diffusion and concentration in the extracellular space (1) and also by back-signaling to neurons directly through the release of neuroactive substances (2). Although glutamate and ATP are the most recognized chemical transmitters that mediate astrocyte-neuron signaling (2), other cell-cell mediators also are involved in this pathway. D-Serine has recently been identified as a major gliotransmitter in the central nervous system that serves as an endogenous ligand for the glycine site of NMDA receptors (3-6).However, many aspects regarding D-serine release still need to be addressed. Although it has been suggested that astrocytes may release D-serine, through the reverse operation of a sodiumdependent transporter (7), the precise molecular mechanisms underlying D-serine release are currently unknown. To unravel the functional consequences of D-serine-mediated astrocyte-toneuron signaling, it is essential to shed light on the mechanisms controlling the gliotransmitter storage and release pathways.For this purpose, we have devised a previously undescribed bioassay to continuously monitor the release of D-serine from cultured glial cells. In this work, we show that astrocytes and C6 glioma cells synthesize and contain a large amount of D-serine that can be released upon glutamate receptor (GluR) stimulation. Moreover, our observations demonstrate that D-serine release, evoked by glutamatergic agonists, is linked to a [Ca 2ϩ...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine

Mothet

Pollegioni

Ouanounou

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

400

350

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“…From these data, we expected that not only glycine but also other factors were involved in the effect of theanine on dopamine concentration in the perfusate. It was shown that glycine is co-localized with GABA in astrocytes and interneurons (Ross and Soltesz 2001;Bureau and Mulle 1998;Xu et al 1999;Levi and Patrizio 1992), and glycine and GABA are released simultaneously and work synergistically on different targets (Bohlhalter et al 1994). We expected that the GABAergic nervous system may also be influenced by theanine injection and is involved in dopamine concentration increase in the perfusate; however we did not examined the effect of theanine on intersutitial GABA concentration and GABA receptors in this study.…”

Section: Discussionmentioning

confidence: 89%

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

et al. 2008

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Theanine (c-glutamylethylamide) is one of the major amino acid components in green tea and can pass through the blood-brain barrier. Recent studies suggest that theanine affects the mammalian central nervous system; however, the detailed mechanism remains unclear. In this study, we demonstrated the effect of theanine on neurotransmission in the brain striatum by in vivo brain microdialysis. Theanine injection into the rat brain striatum did not increase the concentration of excitatory neurotransmitters in the perfusate. On the other hand, theanine injection increased the concentration of glycine in the perfusate. Because it has been reported that theanine promotes dopamine release in the rat striatum, we investigated the glycine and dopamine concentrations in the perfusate. Co-injection of glycine receptor antagonist, strychnine, reduced theanine-induced changes in dopamine. Moreover, AMPA receptor antagonist, which regulates glycine and GABA release from glia cells, inhibited these effects of theanine and this result was in agreement with the known inhibitory effect of theanine at AMPA receptors.

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“…These observations suggest that type 2 astrocytes could play an important role in maintaining the mature CNS. To date, there have been several reports on the biochemical aspects of type 2 astrocytes, such as their endogenous amino acid levels (Levi and Patrizio, 1992), excitatory amino acid receptors (Fan et al, 1999;Gallo et al, 1989), and glutamine synthetase level (Juurlink and Hertz, 1991). However, there are few reports about acidic amino acid transport in type 2 astrocytes because many studies have been performed without classifying the cell type involved.…”

mentioning

confidence: 99%

Acidic Amino Acid Transport Characteristics of a Newly Developed Conditionally Immortalized Rat Type 2 Astrocyte Cell Line (TR-AST).

Tetsuka

Hosoya

Ohtsuki

et al. 2001

Cell Struct. Funct.

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ABSTRACT. To characterize acidic amino acid transport in type 2 astrocytes, we established conditionally immortalized rat astrocyte cell lines (TR-AST) from newly developed transgenic rats harboring temperature-sensitive SV40 large T-antigen gene. TR-AST exhibitedThis study demonstrated that GLT-1, system xC -, and GLAST were expressed in TR-AST, which has the characteristics of type 2 astrocytes and is able to transport acidic amino acids.Key words: acidic amino acid/GLT-1/GLAST/system xC -/transport/type 2 astrocyte Acidic amino acids have conflicting roles at the central nervous system (CNS) because they contribute both to excitatory neurotransmission and excitatory damage (Zorumski and Olney, 1993). Therefore, acidic amino acid transporters in the brain play an important role in maintaining the concentrations below neurotoxic levels (Kanai and Hediger, 1996). System X AG -and system x C -are acidic amino acid transporters, the mRNAs of which are referred to as EAAT (excitatory amino acid transporter) (Palacín et al., 1998), and xCT (Sato et al., 1999), respectively. System X AG -recognizes L-glutamic acid (L-Glu), L-aspartic acid (L-Asp), and D-aspartic acid (D-Asp) in an Na + -dependent manner, while system x C -functions as a complex of xCT and the heavy chain of 4F2 cell surface antigen (4F2hc) protein, accepting L-Glu in an Na + -independent manner, and exchanging L-cystine (Bannai and Kitamura, 1980;Sato et al., 1999).More than a decade ago, two types of astrocytes were found in the rat optic nerve by Raff et al. based on differences in their morphology, cell surface gangliosides, and growth characteristics (Raff et al., 1983). They further con-*To whom correspondence should be addressed: Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.Tel: +81-22-217-6831, Fax: +81-22-217-6886 E-mail: terasaki@mail.pharm.tohoku.ac.jp Abbreviations: 4F2hc, heavy chain of 4F2 cell surface antigen; ALS, amyotrophic lateral sclerosis; CNS, central nervous system; EAAT, excitatory amino acid transporter; GFAP, glial fibrillary acidic protein; GLAST, L-glutamate/L-aspartate transporter; GLT-1, L-glutamate transporter; SV, simian virus; TR-AST, conditionally immortalized rat type 2 astrocyte cell line; tsA58 TG rat, transgenic rat harboring temperature-sensitive SV40 large T-antigen gene.

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Astrocyte Heterogeneity: Endogenous Amino Acid Levels and Release Evoked by Non‐N‐Methyl‐D‐Aspartate Receptor Agonists and by Potassium‐Induced Swelling in Type‐1 and Type‐2 Astrocytes

Cited by 81 publications

References 58 publications

Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine

Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

Acidic Amino Acid Transport Characteristics of a Newly Developed Conditionally Immortalized Rat Type 2 Astrocyte Cell Line (TR-AST).

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