Glial transporters for glutamate, glycine and GABA I. Glutamate transporters

Gadea, Ana; López-Colomé, Ana Marı́a

doi:10.1002/jnr.1039

Cited by 119 publications

(34 citation statements)

References 117 publications

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“…EAAT3 (called EAAC1 in the rodent) is predominantly expressed in the cerebral cortex, basal ganglia and hippocampus. 257 Post-mortem studies in schizophrenic patients revealed alterations in gene expression of glutamate transporters. 258,259 In addition, preclinical studies demonstrated that chronic treatment with clozapine or haloperidol can downregulate EAAT3 in the infralimbic cortex and hippocampal CA2.…”

Section: Dopaminergic Agentsmentioning

confidence: 99%

Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

et al. 2004

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The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act principally on dopamine systems. Many of the second-generation (atypical and dopamine partial agonist) antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the pharmacological properties that confer the different therapeutic effects of the new generation of antipsychotic drugs have remained elusive, and certain side effects can still impact patient health and quality of life. Moreover, the efficacy of antipsychotic drugs is limited prompting the clinical use of adjunctive pharmacy to augment the effects of treatment. In addition, the search for novel and nondopaminergic antipsychotic drugs has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotics, and focuses on novel targets for therapeutic agents for future drug development.

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Section: Dopaminergic Agentsmentioning

confidence: 99%

Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

et al. 2004

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“…Astrocytes predominantly express two transporters that are used in this process: the Lglutamate/L-aspartate transporter (GLAST-1) and the glial L-glutamate transporter (GLT-1), also called excitatory amino acid transporters (EAAT1 and EAAT2, respectively) (Gadea and Lopez-Colome, 2001). Normally, concentration gradients favor the transport of glutamate into astrocytes.…”

Section: Reverse Operation Of Glutamate Transportersmentioning

confidence: 99%

Mechanisms of glutamate release from astrocytes

Malarkey

Parpura

2008

Neurochemistry International

305

216

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Astrocytes can release the excitatory transmitter glutamate which is capable of modulating activity in nearby neurons. This astrocytic glutamate release can occur through six known mechanisms: (i) reversal of uptake by glutamate (ii) anion channel opening induced by cell swelling, (iii) Ca 2+ -dependent exocytosis, (iv) glutamate exchange via the cystine-glutamate antiporter, (v) release through ionotropic purinergic receptors and (vi) functional unpaired connexons, 'hemichannels', on the cell surface. Although these various pathways have been defined, it is not clear how often and to what extent astrocytes employ different mechanisms. It will be necessary to determine whether the same glutamate release mechanisms that operate under physiological conditions operate during pathological conditions or whether there are specific release mechanisms that operate under particular conditions.

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“…Two of these, GLAST and GLT1, dominate glutamate transport in the CNS (Gadea and Lopez-Colome 2001). Drugs are available with specificities that can distinguish GLT1 from GLAST and EAAC1 (Namura et al 2002;Wang et al 1998).…”

Section: Pharmacologymentioning

confidence: 99%

Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

Chen

Kujawa

Sewell

2010

Journal of Neurophysiology

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Chen Z, Kujawa SG, Sewell WF. Functional roles of highaffinity glutamate transporters in cochlear afferent synaptic transmission in the mouse. J Neurophysiol 103: 2581-2586, 2010. First published March 10, 2010 doi:10.1152/jn.00018.2010. In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. L-serine-O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 M for 220 min), TBOA (200 M for 220 min), or SOS (100 M for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noiseinduced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate-or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation.

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Glial transporters for glutamate, glycine and GABA I. Glutamate transporters

Cited by 119 publications

References 117 publications

Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

Mechanisms of glutamate release from astrocytes

Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

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