Stereoselective uptake of the GABA-transaminase inhibitors gamma-vinyl GABA and gamma-acetylenic GABA into neurons and astrocytes.

The cellular uptake of the GABA-transaminase inhibitors gamma-vinyl GABA (GVG) and gamma-acetylenic GABA (GAG) was studied in cultured neurons and astrocytes. By the use of the individual enantiomers R- and S-GVG and R- and S-GAG it could be shown that in both cell types only the S-enantiomers could be actively transported. Comparing neurons and astrocytes only neurons exhibited a high affinity uptake system for S-GVG (Km 78.2 +/- 20.3 microM; Vmax 0.71 +/- 0.06 nmol.min-1.mg-1 cell protein). In case of S-GAG it could not be established with certainty whether the neuronal uptake was of the high affinity type. Both GVG and GAG were studied as inhibitors of GABA uptake into neurons and astrocytes. S-GVG and S-GAG were found to be weak inhibitors of GABA uptake suggesting that S-GVG is not transported by the GABA carrier in neurons. The finding of a much more efficient uptake of S-GVG into neurons than into astrocytes is in line with the previous observation that neuronal GABA-T is more sensitive than astrocytic GABA-T to S-GVG.