Glycine release in the substantia nigra: Interaction with glutamate and GABA

• Published in: Neuropharmacology Vol. 50; no. 5; pp. 548 - 557
• Main Authors: Dopico, José García, González-Hernández, Tomás, Pérez, Ingrid Morales, García, Isabel Gómez, Abril, Antonio Milena, Inchausti, José Obeso, Rodríguez Díaz, Manuel
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2006
• Subjects: Analysis of Variance; Animals; Chromatography, High Pressure Liquid - methods; Citrates - pharmacology; Dose-Response Relationship, Drug; Electrochemistry - methods; Excitatory Amino Acid Agonists - pharmacology; GABA; gamma-Aminobutyric Acid - metabolism; Glutamate; Glutamic Acid - metabolism; Glycine; Glycine - metabolism; Male; Microdialysis - methods; Neuroglia - drug effects; Neuroglia - metabolism; Neurons - drug effects; Neurons - metabolism; Parkinson's disease; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley; Substantia nigra; Substantia Nigra - cytology; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Time Factors; Tritium - metabolism; Zinc; GABA; Parkinson's disease; Glycine; Glutamate; Substantia nigra; Zinc
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2005.10.014

Previous studies have reported a high number of glycine (GLY) receptors in the substantia nigra (SN) but a low number of GLY-neurons, suggesting that taurine, a partial agonist of GLY-receptors, is the natural substrate for SN GLY-receptors. By using microdialysis to quantify amino acids in the extracellular space of the SN, we observed an extracellular pool of GLY in the rat that increased after depolarizing with high-K + in a Ca 2+-dependent manner and that diffuses through the extracellular space. GLY markedly increased after blocking either the tricarboxylic cycle with fluorocitrate or the glutamine synthetase activity with MSO. Because these products act selectively on glial cells, their effects show glia as a key cell in maintaining the extracellular pool of GLY in the SN. Extracellular GLY was modified by glutamate and glutamate receptor agonists. The local administration of GLY modified the extracellular concentration of GABA. Taken together, the complex regulation of the extracellular level of GLY, its possible glial origin and interaction with glutamate and GABA suggest a volume transmitter role for GLY in the SN, a possibility which also agrees with the recent finding of GLY-transporters in this centre.