Elsevier

Brain Research

Volume 608, Issue 1, 9 April 1993, Pages 27-32
Brain Research

Adenosine modulation of amino acid release in rat hippocampus during ischemia and veratridine depolarization

https://doi.org/10.1016/0006-8993(93)90769-JGet rights and content

Abstract

This study was undertaken to determine whether endogenous adenosine modulates ‘in vivo’ neurotransmitter amino acid release via its presynaptic receptors. Two conditions were compared: neuronal depolarization by local infusion of veratridine (600 μM), and transient global ischemia by four-vessel occlusion. Both stimuli were applied for 20 min. Extracellular amino acid (glutamate, taurine/GABA, glycine) variations in concentration were determined in the rat hippocampus by microdialysis and HPLC. Modulation of adenosine receptor activity was objectified by continuous local infusion of an adenosine agonist (R-phenylisopropyladenosine R-PIA) or an antagonist (theophylline), starting one hour before stimulation of amino acid release. R-PIA (100 μM) significantly decreased the glutamate release (50%) evoked by veratridine, whereas it did not significantly modify the ischemia-induced glutamate release. In contrast, theophylline did not significantly affect veratridine-induced glutamate release, but it significantly potentiated glutamate efflux (400%) under ischemic conditions. Neither treatment altered the release of the other amino acids. These data suggest that endogenous adenosine appearing in the extracellular space during veratridine-induced depolarization cannot control glutamate release. In contrast, ischemia-induced glutamate release was strongly inhibited by the concomitant increase in extracellular adenosine.

Reference (36)

  • BenvenisteH. et al.

    Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat

    J. Neurochem.

    (1987)
  • BrunsD.F. et al.

    Adenosine receptor binding: structure activity analysis generates extremely potent xanthine antagonists

  • BustoR. et al.

    Comparative effect of transient global ischemia on extracellular levels of adenosine in vulnerable and non-vulnerable brain regions in the rat

    J. Cereb. Blood Flow Metab.

    (1991)
  • DalyJ.W.

    Adenosine receptors: targets for future drugs

    J. Med. Chem.

    (1982)
  • DrejerJ. et al.

    Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro

    J. Neurochem.

    (1985)
  • FastbomJ. et al.

    Inhibition of [3H]glutamate release from rat hippocampal slices byl-phenylisopropyladenosine

    Acta Physiol. Scand.

    (1985)
  • HoehnK. et al.

    Role of excitatory amino-acid receptors in K+ and glutamate-evoked release of endogenous adenosine from rat cortical slices

    J. Neurochem.

    (1990)
  • KramerG.L. et al.

    Effects of phosphodiesterase inhibitors on cyclic nucleotide levels and relaxation of pig coronary arteries

    Mol. Pharmacol.

    (1979)
  • Cited by (0)

    View full text