ABSTRACT
GLU is the main neurotransmitter in the brain, where it induces a synaptic excitatory action. There is recent evidence for an extracellular nonsynaptic GLU (EnS-GLU) pool in different brain nuclei that, released from glial cells, may act on extrasynaptic GLU receptors of cells located far from the position in which it was released. In the present work, the EnS-GLU pool was studied with microdialysis in the rat substantia nigra (SN). We observed an EnS-GLU pool that increased in a Ca2+-dependent manner during cell depolarization. The selective alteration of with methionine sulfoximide (MSO) and fluorocitrate induced marked modifications in EnS-GLU suggesting that EnS-GLU is dependent on glial cells. Glutamine administration increased GLU, suggesting that neurons are also involved in EnS-GLU modulation. GLU administered in the rostral SN showed a long-distance diffusion to the caudal SN. The ionotropic GLU receptors agonist N-methyl-D-aspartate and kainate and the metabotropic GLU receptors agonist ACPD increased EnS-GLU and decreased extracellular glutamine. Taken together, these data indicate that nigral glia releases GLU, which probably performs a volume transmitter role.
Subject(s)
Extracellular Fluid/metabolism , Glutamic Acid/metabolism , Neuroglia/metabolism , Neurons/metabolism , Substantia Nigra/metabolism , Animals , Calcium/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Citrates/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Extracellular Fluid/drug effects , Glutamic Acid/pharmacology , Glutamine/metabolism , Glutamine/pharmacology , Homeostasis/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Methionine Sulfoximine/pharmacology , Microdialysis , Neuroglia/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Glutamate/drug effects , Receptors, Glutamate/metabolism , Synaptic Transmission/physiology , Up-Regulation/drug effects , Up-Regulation/physiologyABSTRACT
Taurine has been proposed as an inhibitory transmitter in the substantia nigra (SN), but the mechanisms involved in its release and uptake remain practically unexplored. We studied the extracellular pool of taurine in the rat's SN by using microdialysis methods, paying particular attention to the taurine-glutamate (GLU) interaction. Extracellular taurine increased after cell depolarization with high-K(+) in a Ca(2+)-dependent manner, being modified by the local perfusion of GLU, GLU receptor agonists, and zinc. Nigral administration of taurine increased the extracellular concentration of gamma-aminobutyric acid (GABA) and GLU, the transmitters of the two main inputs of the SN. The modification of the glial metabolism with fluocitrate and L-methionine sulfoximine also changed the extracellular concentration of taurine. The complex regulation of the extracellular pool of taurine, its interaction with GABA and GLU, and the involvement of glial cells in its regulation suggest a volume transmission role for taurine in the SN.
