Effects of GABA-analogues on the high-affinity uptake of GABA in astrocytes in primary cultures

Abstract

Employing primary cultures of astrocytes which seem to constitute a valid model of their in vivo counterparts, it has been demonstrated that this cell type is likely to be of importance in terminating the transmitter activity of GABA. It has been shown that the transport carrier in astrocytes is stereospecific for the C-4 hydrogens of the GABA molecule and that its structural requirements are distinct from those exhibited by the neuronal GABA carrier. beta-Proline was a selective inhibitor of GABA transport in astrocytes, whereas R-trans-4-methyl-4-aminocrotonic acid and S-nipecotic acid seemed to be selective inhibitors of neuronal GABA transport, as studied using very thin slices ("prisms") of brain cortex. These findings may be important for studies on the relative significance of the two transport systems in GABA-mediated neurotransmission, and thus for future pharmacological manipulations of the GABA system. This may eventually be beneficial for the treatment of neurological disorders such as epilepsy, Huntington's chorea and Parkinson's disease in which the GABA system seems to be disturbed (34,60,62).