Effects of uptake carrier blockers SK & F 89976-A and L-trans-PDC on in vivo release of amino acids in rat hippocampus.
This report describes the in vivo effects of the uptake carrier blockers 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid hydrochloride (SK & F 89976-A) and L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC) on basal and K(+)-evoked extracellular levels of gamma-aminobutyric acid (GABA), glutamate, aspartate and taurine in the hippocampus of anaesthetised rats, using the microdialysis technique. SK & F 89976-A increased extracellular GABA levels under K(+)-depolarised conditions and did not affect extracellular glutamate, aspartate and taurine levels, indicating its selective effect on GABA uptake L-trans-PDC dose dependently increased basal and K(+)-evoked extracellular glutamate levels, and did not affect extracellular GABA levels, but increased basal aspartate and taurine levels. The K(+)-evoked release of GABA and glutamate, measured in the presence of both SK & F 89976-A and L-trans-PDC, was Ca(2+)-dependent for about 50% and 65%, respectively. In contrast, the release of the putative amino acid transmitters aspartate and taurine was not Ca(2+)-dependent. These results indicate that (1) in rat hippocampus uptake carriers actively regulate extracellular GABA and glutamate levels, (2) the GABA and glutamate released by K+ was derived from both Ca(2+)-dependent (presumably vesicular) and Ca(2+)-independent (presumably cytosolic) pools, whereas aspartate and taurine release was exclusively from Ca(2+)-independent pools.
Zuiderwijk
M
M
Graduate School for the Neurosciences, University of Amsterdam, Netherlands. mzuiderwijk@bio.uva.nl
Veenstra
E
E
Lopes da Silva
F H
FH
Ghijsen
W E
WE
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D011759:Pyrrolidines; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D011188:Potassium; D002118:Calcium