title: Advances in understanding the functions of native GlyT1 and GlyT2 neuronal glycine transporters.
abstract: Glycine can be substrate for two transporters: GlyT1, largely expressed by astrocytes but also by some non-glycinergic neurons, and GlyT2, most frequently present in glycine-storing nerve endings. In morphological studies, GlyT2 expression had been found to be restricted to caudal regions, being almost undetectable in neocortex and hippocampus. Here, we compared the uptake activities of GlyT1 and GlyT2 in synaptosomes purified from mouse spinal cord, cerebellum, neocortex and hippocampus. Although, as expected, [(3)H]glycine uptake was significantly lower in telencephalic than in caudal regions, selective GlyT2-mediated uptake could be evaluated in all areas. Appropriately, [(3)H]glycine selectively taken up into hippocampal synaptosomes through GlyT2 could be subsequently released by exocytosis. Native GlyT2, which did not contribute to basal release from cerebellum or spinal cord nerve terminals, could mediate release of [(3)H]glycine by transporter reversal in synaptosomes exposed to veratridine. Moreover, GlyT2 transporters could perform Na(+)-dependent homoexchange in response to externally added glycine. In conclusion, transporters of the GlyT2 type exhibited significant uptake also in telencephalic regions, probably because of the elevated driving force related to their stoichiometry. Although glycine release through GlyT2 had been predicted to be a very difficult process, GlyT2 expressed on isolated glycinergic nerve terminals can perform both release by transporter reversal and homoexchange.
authors.affiliation: Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.affiliation: Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy. Electronic address: lraiter@pharmatox.unige.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Raiteri
mesh_terms: D000818:Animals; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000502:physiology*; D051379:Mice; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493270:Slc6a5 protein, mouse; C493267:Slc6a9 protein, mouse; D005998:Glycine
keywords: GlyT1; GlyT2; Glycine homoexchange; Glycine transporters; Glycine uptake; Transporter-mediated release