QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (245) Citing Articles via Google Scholar Google Scholar Articles by Swanson, R. A. Articles by Longuemare, M. C. Search for Related Content PubMed PubMed Citation Articles by Swanson, R. A. Articles by Longuemare, M. C.

 Previous Article  |  Next Article 

Volume 17, Number 3, Issue of February 1, 1997 pp. 932-940
Copyright ©1997 Society for Neuroscience

Neuronal Regulation of Glutamate Transporter Subtype Expression in Astrocytes

Received July 11, 1996; revised Oct. 30, 1996; accepted Nov. 7, 1996.

Raymond A. Swanson¹, Jialing Liu¹, Johann W. Miller¹, Jeffrey D. Rothstein², Kevin Farrell¹, Becky A. Stein¹, and Maria C. Longuemare¹

¹ Department of Neurology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121, and ² Deparment of Neuroscience, The Johns Hopkins Medical Center, Baltimore, Maryland 21287

GLT-1, GLAST, and EAAC1 are high-affinity, Na⁺-dependent glutamate transporters identified in rat forebrain. The expression of these transporter subtypes was characterized in three preparations: undifferentiated rat cortical astrocyte cultures, astrocytes cocultured with cortical neurons, and astrocyte cultures differentiated with dibutyryl cyclic AMP (dBcAMP). The undifferentiated astrocyte monocultures expressed only the GLAST subtype. Astrocytes cocultured with neurons developed a stellate morphology and expressed both GLAST and GLT-1; neurons expressed only the EAAC1 transporter, and rare microglia in these cultures expressed GLT-1. Treatment of astrocyte cultures with dBcAMP induced expression of GLT-1 and increased expression of GLAST. These effects of dBcAMP on transporter expression were qualitatively similar to those resulting from coculture with neurons, but immunocytochemistry showed the pattern of transporter expression to be more complex in the coculture preparations. Compared with astrocytes expressing only GLAST, the dBcAMP-treated cultures expressing both GLAST and GLT-1 showed an increase in glutamate uptake V_max, but no change in the glutamate K_m and no increased sensitivity to inhibition by dihydrokainate. Pyrrolidine-2,4-dicarboxylic acid and threo--hydroxyaspartic acid caused relatively less inhibition of transport in cultures expressing both GLAST and GLT-1, suggesting a weaker effect at GLT-1 than at GLAST. These studies show that astrocyte expression of glutamate transporter subtypes is influenced by neurons, and that dBcAMP can partially mimic this influence. Manipulation of transporter expression in astrocyte cultures may permit identification of factors regulating the expression and function of GLAST and GLT-1 in their native cell type.

Key words: dibutyryl cAMP; dihydrokainate; GLT-1; threo--hydroxyaspartate; glutamate uptake; PDC; pyrrolidine-2,4-dicarboxylate; microglia; GLAST

This article has been cited by other articles:

				M. R. Regan, Y. H. Huang, Y. S. Kim, M. I. Dykes-Hoberg, L. Jin, A. M. Watkins, D. E. Bergles, and J. D. Rothstein Variations in Promoter Activity Reveal a Differential Expression and Physiology of Glutamate Transporters by Glia in the Developing and Mature CNS J. Neurosci., June 20, 2007; 27(25): 6607 - 6619. [Abstract] [Full Text] [PDF]

				D. B. Kintner, J. Luo, J. Gerdts, A. J. Ballard, G. E. Shull, and D. Sun Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1113 - C1122. [Abstract] [Full Text] [PDF]

				G. Tian, L. Lai, H. Guo, Y. Lin, M. E. R. Butchbach, Y. Chang, and C.-l. G. Lin Translational Control of Glial Glutamate Transporter EAAT2 Expression J. Biol. Chem., January 19, 2007; 282(3): 1727 - 1737. [Abstract] [Full Text] [PDF]

				K. Chu, S.-T. Lee, D.-I. Sinn, S.-Y. Ko, E.-H. Kim, J.-M. Kim, S.-J. Kim, D.-K. Park, K.-H. Jung, E.-C. Song, et al. Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation Stroke, January 1, 2007; 38(1): 177 - 182. [Abstract] [Full Text] [PDF]

				G. Gras, F. Porcheray, B. Samah, and C. Leone The glutamate-glutamine cycle as an inducible, protective face of macrophage activation J. Leukoc. Biol., November 1, 2006; 80(5): 1067 - 1075. [Abstract] [Full Text] [PDF]

				W. Boston-Howes, S. L. Gibb, E. O. Williams, P. Pasinelli, R. H. Brown Jr., and D. Trotti Caspase-3 Cleaves and Inactivates the Glutamate Transporter EAAT2 J. Biol. Chem., May 19, 2006; 281(20): 14076 - 14084. [Abstract] [Full Text] [PDF]

				D. B. Kintner, A. Look, G. E. Shull, and D. Sun Stimulation of astrocyte Na+/H+ exchange activity in response to in vitro ischemia depends in part on activation of ERK1/2 Am J Physiol Cell Physiol, October 1, 2005; 289(4): C934 - C945. [Abstract] [Full Text] [PDF]

				B. Lenart, D. B. Kintner, G. E. Shull, and D. Sun Na-K-Cl Cotransporter-Mediated Intracellular Na+ Accumulation Affects Ca2+ Signaling in Astrocytes in an In Vitro Ischemic Model J. Neurosci., October 27, 2004; 24(43): 9585 - 9597. [Abstract] [Full Text] [PDF]

				M. E. R. Butchbach, G. Tian, H. Guo, and C.-l. G. Lin Association of Excitatory Amino Acid Transporters, Especially EAAT2, with Cholesterol-rich Lipid Raft Microdomains: IMPORTANCE FOR EXCITATORY AMINO ACID TRANSPORTER LOCALIZATION AND FUNCTION J. Biol. Chem., August 13, 2004; 279(33): 34388 - 34396. [Abstract] [Full Text] [PDF]

				D. B. Kintner, G. Su, B. Lenart, A. J. Ballard, J. W. Meyer, L. L. Ng, G. E. Shull, and D. Sun Increased tolerance to oxygen and glucose deprivation in astrocytes from Na+/H+ exchanger isoform 1 null mice Am J Physiol Cell Physiol, July 1, 2004; 287(1): C12 - C21. [Abstract] [Full Text] [PDF]

				M. I. Gonzalez and M. B. Robinson Protein KINASE C-Dependent Remodeling of Glutamate Transporter Function Mol. Interv., February 1, 2004; 4(1): 48 - 58. [Abstract] [Full Text] [PDF]

				E. Solenov, H. Watanabe, G. T. Manley, and A. S. Verkman Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method Am J Physiol Cell Physiol, February 1, 2004; 286(2): C426 - C432. [Abstract] [Full Text]

				N.-J. Xu, L. Bao, H.-P. Fan, G.-B. Bao, L. Pu, Y.-J. Lu, C.-F. Wu, X. Zhang, and G. Pei Morphine Withdrawal Increases Glutamate Uptake and Surface Expression of Glutamate Transporter GLT1 at Hippocampal Synapses J. Neurosci., June 1, 2003; 23(11): 4775 - 4784. [Abstract] [Full Text] [PDF]

				D. J. Rademacher, S. Patel, F. A. Hopp, C. Dean, C. J. Hillard, and J. L. Seagard Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1570 - H1576. [Abstract] [Full Text] [PDF]

				Z.-z. Su, M. Leszczyniecka, D.-c. Kang, D. Sarkar, W. Chao, D. J. Volsky, and P. B. Fisher Insights into glutamate transport regulation in human astrocytes: Cloning of the promoter for excitatory amino acid transporter 2 (EAAT2) PNAS, February 18, 2003; 100(4): 1955 - 1960. [Abstract] [Full Text] [PDF]

				S. Duan, C. M. Anderson, E. C. Keung, Y. Chen, Y. Chen, and R. A. Swanson P2X7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes J. Neurosci., February 15, 2003; 23(4): 1320 - 1328. [Abstract] [Full Text] [PDF]

				J. Mao, B. Sung, R.-R. Ji, and G. Lim Chronic Morphine Induces Downregulation of Spinal Glutamate Transporters: Implications in Morphine Tolerance and Abnormal Pain Sensitivity J. Neurosci., September 15, 2002; 22(18): 8312 - 8323. [Abstract] [Full Text] [PDF]

				P. F. Behrens, P. Franz, B. Woodman, K. S. Lindenberg, and G. B. Landwehrmeyer Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation Brain, August 1, 2002; 125(8): 1908 - 1922. [Abstract] [Full Text] [PDF]

				K. R. G. Martin, H. Levkovitch-Verbin, D. Valenta, L. Baumrind, M. E. Pease, and H. A. Quigley Retinal Glutamate Transporter Changes in Experimental Glaucoma and after Optic Nerve Transection in The Rat Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2236 - 2243. [Abstract] [Full Text] [PDF]

				C.-S. Yuan, L. Dey, J.-T. Xie, and H. H. Aung Pharmacology and toxicology of astrocyte-neuron glutamate transport and cycling. J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 1 - 6. [Abstract] [Full Text] [PDF]

				W. Chen, C. Aoki, V. Mahadomrongkul, C. E. Gruber, G. J. Wang, R. Blitzblau, N. Irwin, and P. A. Rosenberg Expression of a Variant Form of the Glutamate Transporter GLT1 in Neuronal Cultures and in Neurons and Astrocytes in the Rat Brain J. Neurosci., March 15, 2002; 22(6): 2142 - 2152. [Abstract] [Full Text] [PDF]

				K. Suzuki, Y. Ikegaya, S. Matsuura, Y. Kanai, H. Endou, and N. Matsuki Transient upregulation of the glial glutamate transporter GLAST in response to fibroblast growth factor, insulin-like growth factor and epidermal growth factor in cultured astrocytes J. Cell Sci., March 12, 2002; 114(20): 3717 - 3725. [Abstract] [Full Text] [PDF]

				E. A. Proper, G. Hoogland, S. M. Kappen, G. H. Jansen, M. G. A. Rensen, L. H. Schrama, C. W. M. van Veelen, P. C. van Rijen, O. van Nieuwenhuizen, W. H. Gispen, et al. Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy Brain, January 1, 2002; 125(1): 32 - 43. [Abstract] [Full Text] [PDF]

				J. Leonova, T. Thorlin, N. D. Aberg, P. S. Eriksson, L. Ronnback, and E. Hansson Endothelin-1 decreases glutamate uptake in primary cultured rat astrocytes Am J Physiol Cell Physiol, November 1, 2001; 281(5): C1495 - C1503. [Abstract] [Full Text] [PDF]

				G. Su, R. A. Haworth, R. J. Dempsey, and D. Sun Regulation of Na+-K+-Cl- cotransporter in primary astrocytes by dibutyryl cAMP and high [K+]o Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1710 - C1721. [Abstract] [Full Text] [PDF]

				V W Pentreath and N D Slamon Astrocyte phenotype and prevention against oxidative damage in neurotoxicity Human and Experimental Toxicology, November 1, 2000; 19(11): 641 - 649. [Abstract] [PDF]

				M. Figiel and J. Engele Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), a Neuron-Derived Peptide Regulating Glial Glutamate Transport and Metabolism J. Neurosci., May 15, 2000; 20(10): 3596 - 3605. [Abstract] [Full Text] [PDF]

				O. Zelenaia, B. D. Schlag, G. E. Gochenauer, R. Ganel, W. Song, J. S. Beesley, J. B. Grinspan, J. D. Rothstein, and M. B. Robinson Epidermal Growth Factor Receptor Agonists Increase Expression of Glutamate Transporter GLT-1 in Astrocytes through Pathways Dependent on Phosphatidylinositol 3-Kinase and Transcription Factor NF-kappa B Mol. Pharmacol., April 1, 2000; 57(4): 667 - 678. [Abstract] [Full Text]

				Y. H. Gong, A. S. Parsadanian, A. Andreeva, W. D. Snider, and J. L. Elliott Restricted Expression of G86R Cu/Zn Superoxide Dismutase in Astrocytes Results in Astrocytosis But Does Not Cause Motoneuron Degeneration J. Neurosci., January 15, 2000; 20(2): 660 - 665. [Abstract] [Full Text] [PDF]

				S. Duan, C. M. Anderson, B. A. Stein, and R. A. Swanson Glutamate Induces Rapid Upregulation of Astrocyte Glutamate Transport and Cell-Surface Expression of GLAST J. Neurosci., December 1, 1999; 19(23): 10193 - 10200. [Abstract] [Full Text] [PDF]

				J. Masson, C. Sagne, M. Hamon, and S. E. Mestikawy Neurotransmitter Transporters in the Central Nervous System Pharmacol. Rev., September 1, 1999; 51(3): 439 - 464. [Abstract] [Full Text] [PDF]

				J. Tan, O. Zelenaia, D. Correale, J. D. Rothstein, and M. B. Robinson Expression of the GLT-1 Subtype of Na+-Dependent Glutamate Transporter: Pharmacological Characterization and Lack of Regulation by Protein Kinase C J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1600 - 1610. [Abstract] [Full Text]

				S. Mennerick, R. P. Dhond, A. Benz, W. Xu, J. D. Rothstein, N. C. Danbolt, K. E. Isenberg, and C. F. Zorumski Neuronal Expression of the Glutamate Transporter GLT-1 in Hippocampal Microcultures J. Neurosci., June 15, 1998; 18(12): 4490 - 4499. [Abstract] [Full Text] [PDF]

				B. D. Schlag, J. R. Vondrasek, M. Munir, A. Kalandadze, O. A. Zelenaia, J. D. Rothstein, and M. B. Robinson Regulation of the Glial Na+-Dependent Glutamate Transporters by Cyclic AMP Analogs and Neurons Mol. Pharmacol., March 1, 1998; 53(3): 355 - 369. [Abstract] [Full Text]

				G. J. Wang, H. J. Chung, J. Schnuer, K. Pratt, A. C. Zable, M. P. Kavanaugh, and P. A. Rosenberg High Affinity Glutamate Transport in Rat Cortical Neurons in Culture Mol. Pharmacol., January 1, 1998; 53(1): 88 - 96. [Abstract] [Full Text]

				A. Furuta, J. D. Rothstein, and L. J. Martin Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development J. Neurosci., November 1, 1997; 17(21): 8363 - 8375. [Abstract] [Full Text] [PDF]

				G. Gegelashvili and A. Schousboe High Affinity Glutamate Transporters: Regulation of Expression and Activity Mol. Pharmacol., July 1, 1997; 52(1): 6 - 15. [Abstract] [Full Text]

				D. Trotti, M. Aoki, P. Pasinelli, U. V. Berger, N. C. Danbolt, R. H. Brown Jr., and M. A. Hediger Amyotrophic Lateral Sclerosis-linked Glutamate Transporter Mutant Has Impaired Glutamate Clearance Capacity J. Biol. Chem., January 5, 2001; 276(1): 576 - 582. [Abstract] [Full Text] [PDF]

				M. Daniels and D. R. Brown Astrocytes Regulate N-Methyl-D-aspartate Receptor Subunit Composition Increasing Neuronal Sensitivity to Excitotoxicity J. Biol. Chem., June 15, 2001; 276(25): 22446 - 22452. [Abstract] [Full Text] [PDF]

				G. Su, D. B. Kintner, and D. Sun Contribution of Na+-K+-Cl- cotransporter to high-[K+]o- induced swelling and EAA release in astrocytes Am J Physiol Cell Physiol, May 1, 2002; 282(5): C1136 - C1146. [Abstract] [Full Text] [PDF]

				G. Su, D. B. Kintner, M. Flagella, G. E. Shull, and D. Sun Astrocytes from Na+-K+-Cl- cotransporter-null mice exhibit absence of swelling and decrease in EAA release Am J Physiol Cell Physiol, May 1, 2002; 282(5): C1147 - C1160. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help