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(Stroke. 1996;27:941-950.)
© 1996 American Heart Association, Inc.
Articles |
Relationships Between ATP Depletion, Membrane Potential, and the Release of Neurotransmitters in Rat Nerve Terminals
An In Vitro Study Under Conditions That Mimic Anoxia, Hypoglycemia, and Ischemia
From Centro de Neurociências de Coimbra, Departamento de Zoologia, Universidade de Coimbra (Portugal).
Correspondence to M.S. Santos, Centro de Biologia Celular, Departamento de Zoologia, Universidade de Coimbra, 3049 Coimbra Codex, Portugal.
Background and Purpose It is known that the extracellular accumulation of glutamate during anoxia/ischemia is responsible for initiating neuronal injury. However, little information is available on the release of monoamines and whether the mechanism of its release resembles that of glutamate, which may itself influence the release of monoamines by activating presynaptic receptors. This study was designed to characterize the release of both amino acids and monoamines under chemical conditions that mimic anoxia, hypoglycemia, and ischemia.
Methods The contents of synaptosomes in adenine
nucleotides (ATP, ADP, and AMP), amino acids (aspartate,
glutamate, taurine, and 
-aminobutyric acid), and monoamines
(dopamine, noradrenaline, and
5-hydroxytryptamine) were measured by
high-performance liquid chromatography,
after the synaptosomes were subjected to anoxia (KCN+oligomycin),
hypoglycemia (2 mmol/L 2-deoxyglucose in glucose-free medium), and
ischemia (anoxia plus hypoglycemia).
Results The anoxia- and ischemia-induced release of noradrenaline, dopamine, 5-hydroxytryptamine, and glutamate correlated well with ATP depletion. The correlation observed between glutamate levels and the release of dopamine and 5-hydroxytryptamine in ischemic conditions suggests a functional linkage between the two transmitter systems. However, the antagonists of presynaptic glutamate receptors failed to alter the amount of monoamines released. The inhibition of Na+,K+-ATPase by ouabain had an effect similar to that produced by ischemia.
Conclusions The decrease in Na+ and K+ gradients resulting from the energy depletion of the synaptosomes under ischemic conditions or resulting from the inhibition of Na+,K+-ATPase by ouabain promotes the reversal of the neurotransmitter transporters. The decrease in uptake of neurotransmitters may also contribute to the rise in the extracellular concentration of different transmitters observed during brain ischemia.
Key Words: anoxia • cerebral ischemia • glutamates • hypoglycemia • neuronal damage • neurotransmitters • rats
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