Glycine-induced long-term synaptic potentiation is mediated by the glycine transporter GLYT1.

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Igartua I, Solis JM, Bustamante J

Glycine-induced long-term synaptic potentiation is mediated by the glycine transporter GLYT1.

Neuropharmacology. 2007 Jun;52(8):1586-95. Epub 2007 Mar 14.

PubMed ID

17462677 [ View in PubMed

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Abstract

The negative symptoms of schizophrenia are reverted by treatment with glycine or other agonists of the glycine-B site which facilitate NMDA receptor function. On the other hand, there are experimental observations showing that exogenous application of glycine (0.5-10mM) results in a long-lasting potentiation of glutamatergic synaptic transmission (LTP-GLY). The characterization of the mechanisms underlying LTP-GLY could be useful to develop new therapies for schizophrenia. The main goal of this work is to deepen the understanding of this potentiation phenomenon. The present study demonstrates in rat hippocampal slices that superfusion of glycine 1mM during 30 min produces a potentiation of excitatory postsynaptic potentials in CA3-CA1 pathway lasting at least 1h. Glycine application does not modify neither presynaptic fiber volley nor paired-pulse facilitation of synaptic potentials. This LTP-GLY is independent of both strychnine-sensitive glycine receptors and nifedipine-sensitive calcium channels. Interestingly, LTP-GLY is not inhibited but strengthened by NMDA receptors antagonists such as AP-5 or MK-801. In contrast, LTP-GLY is partially or totally blocked with the antagonists of glycine transporter GLYT1, sarcosine or ALX-5407, respectively. These results indicate that LTP-GLY requires the activation of GLYT1, a glycine transporter co-localized and associated to NMDA receptors. In addition, the fact that NMDA receptor inhibition increases LTP-GLY magnitude, opens the possibility that these receptors could have a negative control on GLYT1 activity.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Glycine	Sodium- and chloride-dependent glycine transporter 1	Protein	Humans	Unknown	Substrate	Details