Structure, function and regulation of glycine neurotransporters

Glycine exerts multiple functions in the central nervous system, as an inhibitory neurotransmitter through activation of specific, Cl-permeable, ligand-gated ionotropic receptors and as an obligatory co-agonist with glutamate on the activation of N-methyl-D-aspartate (NMDA) receptors. In some areas of the central nervous system, glycine seems to be co-released with gamma-aminobutyric acid (GABA), the main inhibitory amino acid neurotransmitter. The synaptic action of glycine ends by active recapture through sodium- and chloride-coupled glycine transporters located in glial and neuronal plasma membranes, whose structure-function relationship is being studied. The trafficking and plasma membrane expressions of these proteins are controlled by regulatory mechanisms. Glycine transporter inhibitors may find application in the treatment of muscle tone defects, epilepsy, schizophrenia, pain and neurodegenerative disorders. This review deals on recent progress on localization, transport mechanisms, structure, regulation and pharmacology of the glycine transporters (GLYTs). (C) 2003 Elsevier B.V. All rights reserved.