A microdialysis study in rat brain of dihydrokainate, a glutamate uptake inhibitor.
Microdialysis in neostriatum of anaesthetized rats was performed to study effects on amino acid efflux of the glutamate uptake-inhibitor dihydrokainate (DHK). Both basal and K+-evoked (100 mM) efflux of glutamate increased in the presence of DHK. The increase in the basal glutamate efflux occurred at lower DHK concentrations than during K+-depolarization (when the extracellular glutamate concentration was several-fold higher), confirming that DHK is a competitive inhibitor. The increase in basal efflux caused by DHK did not exhibit Ca(2+)-dependency, whereas 50% of the increase in glutamate efflux during K+-depolarization was Ca(2+)-dependent. The Ca(2+)-dependent efflux is related to transmitter release, whereas the Ca(2+)-independent efflux is probably due to metabolic events and/or transport of DHK into cells in exchange for glutamate. Taurine efflux in response to DHK increased both during basal conditions and K+-depolarization, probably secondary to the increase in glutamate concentration, whereas aspartate, GABA, glutamine and alanine effluxes did not change.
Fallgren
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Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
Paulsen
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D000818:Animals; D002118:Calcium / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects*; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D018698:Glutamic Acid; C020889:dihydrokainic acid; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium