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

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Abstract

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 enantiomersR- andS-GVG andR- andS-GAG it could be shown that in both cell types only theS-enantiomers could be actively transported. Comparing neurons and astrocytes only neurons exhibited a high affinity uptake system forS-GVG (K m 78.2±20.3 μM;V max 0.71±0.06 nmol · min−1 · mg−1 cell protein). In case ofS-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 andS-GAG were found to be weak inhibitors of GABA uptake suggesting thatS-GVG is not transported by the GABA carrier in neurons. The finding of a much more efficient uptake ofS-GVG into neurons than into astrocytes is in line with the previous observation that neuronal GABA-T is more sensitive than astrocytic GABA-T toS-GVG.

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Authors and Affiliations

  1. Department of Biochemistry A, Panum Institute, University of Copenhagen, 3 Blegdamsvej, DK-2200, Copenhagen, Denmark

    Arne Schousboe

  2. Department of Biology, Royal Danish School of Pharmacy, DK-2100, Copenhagen, Denmark

    Orla M. Larsson

  3. Merrell Dow Research Institute, Strasbourg Center, 67084, Strasbourg Cedex, France

    Nikolaus Seiler

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  1. Arne Schousboe
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  2. Orla M. Larsson
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Schousboe, A., Larsson, O.M. & Seiler, N. Stereoselective uptake of the GABA-transaminase inhibitors gamma-vinyl gaba and gamma-acetylenic GABA into neurons and astrocytes. Neurochem Res 11, 1497–1505 (1986). https://doi.org/10.1007/BF00965769

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