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Lessons from the Knocked-Out Glycine Transporters

  • Chapter
Neurotransmitter Transporters

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 175))

Abstract

Glycine has multiple neurotransmitter functions in the central nervous system (CNS). In the spinal cord and brainstem of vertebrates, it serves as a major inhibitory neurotransmitter. In addition, it participates in excitatory neurotransmission by modulating the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors. The extracellular concentrations of glycine are regulated by Na+/Cl−-dependent glycine transporters (GlyTs), which are expressed in neurons and adjacent glial cells. Considerable progress has been made recently towards elucidating the in vivo roles of GlyTs in the CNS. The generation and analysis of animals carrying targeted disruptions of GlyT genes (GlyT knockoutmice) have allowed investigators to examine the different contributions of individual GlyT subtypes to synaptic transmission. In addition, they have provided animal models for two hereditary human diseases, glycine encephalopathy and hyperekplexia. Selective GlyT inhibitors have been shown to modulate neurotransmission and might constitute promising therapeutic tools for the treatment of psychiatric and neurological disorders such as schizophrenia and pain. Therefore, pharmacological and genetic studies indicate that GlyTs are key regulators of both glycinergic inhibitory and glutamatergic excitatory neurotransmission. This chapter describes our present understanding of the functions of GlyTs and their involvement in the fine-tuning of neuronal communication.

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Authors and Affiliations

  1. Department of Pharmacology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark

    J. Gomeza

  2. Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528, Frankfurt, Germany

    W. Armsen, H. Betz & V. Eulenburg

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  3. H. Betz
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  4. V. Eulenburg
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  1. Institute of Pharmacology Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Waehringer Str. 13a, A-1090, Wien, Austria

    Harald H. Sitte  & Michael Freissmuth  & 

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Gomeza, J., Armsen, W., Betz, H., Eulenburg, V. (2006). Lessons from the Knocked-Out Glycine Transporters. In: Sitte, H.H., Freissmuth, M. (eds) Neurotransmitter Transporters. Handbook of Experimental Pharmacology, vol 175. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29784-7_19

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