title: Glycine release from astrocytes via functional reversal of GlyT1.
abstract: It was previously reported that functional glycine receptors were expressed in neonatal prefrontal cortex; however, the glycine-releasing cells were unknown. We hypothesized that astrocytes might be a major glycine source, and examined the glycine release properties of astrocytes. We also hypothesized that dopamine (DA) might be a trigger for the astrocytic glycine release, as numerous DA terminals localize in the cortex. We combined two different methods to confirm the glycine release from astrocytes. Firstly, we analyzed the supernatant of astrocytes by amino acid analyzer after DA stimulation, and detect significant glycine peak. Furthermore, we utilized a patch-clamp biosensor method to confirm the glycine release from astrocytes by using GlyRα1 and Glyβ-expressing HEK293T cells, and detected significant glycine-evoked current upon DA stimulation. Thus, we clearly demonstrated that DA induces glycine release from astrocytes. Surprisingly, DA caused a functional reversal of astrocytic glycine transporter 1, an astrocytic type of glycine transporter, causing astrocytes to release glycine. Hence, astrocytes transduce pre-synaptic DA signals to glycine signals through a reversal of astrocytic glycine transporter 1 to regulate neuronal excitability. Cover Image for this issue: doi: 10.1111/jnc.13785.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.|Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.|Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Japan.|Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
authors.affiliation: Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Hosoi
authors.affiliation: Bioresource Center, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.affiliation: Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.|Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Japan.|Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Physiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D005998:Glycine; D004298:Dopamine
keywords: GlyT1; astrocyte; glia; gliotransmitter; glycine