Mechanisms of Glycine Release in Mouse Brain Stem Slices |
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Authors: | Pirjo Saransaari Simo S Oja |
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Institution: | (1) Tampere Brain Research Center, Medical School, University of Tampere, 33014 Tampere, Finland;(2) Department of Paediatrics, Tampere University Hospital, Tampere, Finland |
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Abstract: | In the brain stem glycine is associated with multiple sensory and visceral regulations, being involved in, for instance, cardiovascular,
respiratory and auditory functions. We here studied the mechanisms of the release of preloaded 3H]glycine from mouse brain stem slices in a superfusion system. A depolarizing concentration of K+ ions (50 mM) evoked glycine release, but in the absence of Ca2+ the effect was attenuated, indicating that a part of the evoked release represents Ca2+-dependent exocytosis. The Ca2+-independent release was enhanced by omission of Na+ and Cl−. The stimulatory effect of extracellular glycine confirmed the involvement of transporters functioning in a reverse direction.
A part of the release is mediated by Na+ and Cl− channels, since it was inhibited by the inhibitors of these, riluzole and 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonate,
respectively. Glycine release was potentiated by the activation of protein kinase C and diminished by increasing cyclic guanosine
monophosphate levels with a phosphodiesterase inhibitor, zaprinast. The release was also modulated by the phospholipase inhibitor
quinacrine and the tyrosine kinase inhibitor genistein. Adenosine A1 receptors likewise regulate glycine release, since it was enhanced by their agonist R(−)N6-(2-phenylisopropyl)adenosine, which effect was blocked by the antagonist 8-cyclopentyl-1,3-dipropylxanthine. The ionotropic
glutamate receptor agonists N-methyl-d-aspartate, kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate failed to have any effects contrary to their effects
in higher brain regions, e.g., in the hippocampus. The group I and III metabotropic glutamate receptor agonists (S)-3,5-dihydroxyphenylglycine
and O-phospho-l-serine, respectively, increased the release in a receptor-mediated manner. Glycine release in the brain stem was also markedly
enhanced by cell-damaging conditions, including hypoxia, hypoglycemia and ischemia. |
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Keywords: | Glycine release Potassium stimulation Ion channels Protein kinase C Phospholipases Adenosine receptors Glutamate receptors Cell-damaging conditions Brain stem slices Developing and adult mice |
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