The in vivo inactivation of GABA and other inhibitory amino acids in the cat nervous system

Abstract

In cats anaesthetised with pentobarbitone, the effect of inhibitors of the in vitro cellular uptake of GABA were tested on the responses of single central neurones to GABA and other depressant amino acids. (4)- AND (-)-nepecotic acid, (4)-2,4-diaminobutyric acid (DABA) and 2,2-dimethyl-beta-alanine, enhanced the action of GABA on spinal, cerebellar and cerebral cortical neurones. In the spinal cord DABA, and to a less estent (-)-nipecotic acid, enhanced the action of beta-alanine, whereas the actions of glycine and taurine were unaffected by DABA and reduced by (-)-nipecotic acid. In the cerebellum and cerebral cortex, these two substances enhanced the action of GABA, usually to a greater extent than that of beta-alanine and taurine, although this specificity was not marked. The GABA-mediated basket cell inhibition of Purkinje cells in the cerebellum was unaffected by DABA and (-)-nipecotic acid, and neither substance appears suitable for determining the role of uptake processes in the inactivation of synapitcally released GABA. Quantitatively these in vivo results agree more closely with recent vitro uptake studies in cat tissue than the previously published data on rat cerebral cortex and dorsal root ganglia, and the observations provide further evidence for the importance of cellular uptake in maintaining low extraneuronal concentrations of inhibitory amino acid transmitters.