Comparison of effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [H-3]D-aspartate in astrocytes and glutamatergic neurons

Uptake and release processes in cerebellar astrocytes and granule neurons ( glutamatergic) for glutamate were investigated by the use of [H-3]D-asparta te. a non-metabolizable glutamate analog. The effects of DL-threo-beta -ben zyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4- PDC) on uptake and release of [H-3]D-aspartate were studied. Both compounds inhibited potently uptake of [H-3]D-aspartate in neurons and astrocyteS (I C50 values 10-100 muM), DL-TBOA being slightly more potent than t-2,4-PDC. Release of preloaded [H-3]D-aspartate from neurons or astrocytes could be s timulated by addition of excess t-2,4-PDC whereas addition of DL-TBOA had n o effect on [H-3]D-aspartate efflux. Moreover, DL-TBOA inhibited significan tly the depolarization-induced (55 mM KCl) release of preloaded [H-3]D-aspa rtate in the neurons. The results reflect the fact that DL-TBOA is not tran sported by the glutamate carriers while t-2,4-PDC is a substrate which may heteroexchange with [H-3]D-aspartate. It is suggested that DL-TBOA may be u sed to selectively inhibit depolarization coupled glutamate release mediate d by reversal of the carriers.