Release of endogenous glutamate from rat cortical slices in presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid.
The effect of the new glutamate uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), on the electrically evoked release or, rather, overflow of endogenous glutamate in superfusates from rat cortical slices was compared with that of dihydrokainate. In the absence of these presumed uptake inhibitors, electrical stimulation for 4 min at 1 Hz did not elicit a measurable glutamate overflow over baseline at all. Basal overflow increased concentration-dependently in the presence of 10-100 microM L-trans-PDC, about 5-fold at 100 microM. Also, electrical stimulation caused increases of glutamate overflow over basal levels progressive with increasing concentrations of trans-PDC; a stimulated overflow corresponding to about 50% of basal overflow was obtained at 100 microM. Basal as well as evoked release in the presence of dihydrokainate did not exceed ca. 60% of that obtained with 100 microM L-trans-PDC. In synaptosomes, L-trans-PDC much more than dihydrokainate caused a transient increase of spontaneous glutamate release which was diminished in the absence of Na+, indicating that it is transported into the cytoplasm by the glutamate carrier and induces some efflux of the amino acid from this compartment. Moreover, trans-PDC caused a weak to moderate inhibition of K(+)-evoked glutamate release from synaptosomes at 10-300 microM, without obvious concentration-dependence. Glutamate overflow elicited from rat cortical slices by electrical field stimulation at 1 Hz was Ca(2+)-dependent to about 80%. Tetrodotoxin (0.3 microM) reduced it by about 90%.(ABSTRACT TRUNCATED AT 250 WORDS)
Waldmeier
P C
PC
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Wicki
P
P
Feldtrauer
J J
JJ
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004558:Electric Stimulation; D058788:GABA-B Receptor Antagonists; D005971:Glutamates / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D003998:Dicarboxylic Acids; D058788:GABA-B Receptor Antagonists; D005971:Glutamates; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010721:Phosphinic Acids; D011412:Propanolamines; D011759:Pyrrolidines; C085075:CGP 55845A; D013779:Tetrodotoxin; C020889:dihydrokainic acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D001418:Baclofen; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium