EFFECTS OF UPTAKE CARRIER BLOCKERS SK-AND-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 blocke rs 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid hydrochlori de (SK&F 89976-A) and L-trans-pynolidine-2,4-dicarboxylate (L-trans-PD C) on basal and K+-evoked extracellular levels of gamma-aminobutyric a cid (GABA), glutamate, aspartate and taurine in the hippocampus of ana esthetised rats, using the microdialysis technique. SK&F 89976-A incre ased extracellular GABA levels under K+-depolarised conditions and did not affect extracellular glutamate, aspartate and taurine levels, ind icating its selective effect on GABA uptake. L-trans-PDC dose dependen tly increased basal and K+-evoked extracellular glutamate levels, and did not affect extracellular GABA levels, but increased basal aspartat e and taurine levels. The K+-evoked release of GABA and glutamate, mea sured in the presence of both SK&F 89976-A and L-trans-PDC, was Ca2+-d ependent for about 50% and 65%, respectively. In contrast, the release of the putative amino acid transmitters aspartate and taurine was not Ca2+-dependent. These results indicate that (1) in rat hippocampus up take carriers actively regulate extracellular GABA and glutamate level s, (2) the GABA and glutamate released by K+ was derived from both Ca2 +-dependent (presumably vesicular) and Ca2+-independent (presumably cy tosolic) pools, whereas aspartate and taurine release was exclusively from Ca2+-independent pools.