Adenosine modulation of amino acid release in rat hippocampus during ischemia and veratridine depolarization.
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 microM), 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 microM) 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.
Laboratoire de Recherches Cérébrovasculaires, UA 641 CNRS, Université Paris VII, France.
A
A
Heron
F
F
Lasbennes
J
J
Seylaz
D000241:Adenosine / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003956:Dialysis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007263:Infusions, Parenteral; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008846:Micromanipulation; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*
D000596:Amino Acids; D010660:Phenylisopropyladenosine; D014701:Veratridine; D013806:Theophylline; D000241:Adenosine