Pentobarbital: Differential effects on the depolarization-induced release of excitatory and inhibitory amino acids from cerebral cortex slices

Abstract

Guinea pig cerebral cortex slices were used to investigate the effects of pentobarbital on the release, uptake, and metabolism of transmitter and other amino acids. Slices were allowed to metabolize D-(U- 14C) glucose. Subsequent electrical stimulation resulted in a relatively large release, probably from nerve terminals, of endogenously labelled 14C-glutamate, 14C-aspartate, and 14C-GABA, as well as a relatively, small release, probably not from nerve terminals, of 14C-alanine, 14C-glycine, and 14C-threonine-serine-glutamine (unseparated). Pentobarbital (0.1 mM) inhibited the release of 14C-glutamate and 14C-aspartate by 30–40%, increased the release of 14C-GABA by 25%, and had no effect on the release of the other endogenously labelled amino acids. It had no effect on the stimulated release of exogenous glutamate, aspartate and GABA, previously taken up from the medium. Effects on the stimulated release of endogenously labelled glutamate, aspartate, and GABA could not be attributed to altered tissue levels of these amino acids or to changes in the rates of their synthesis, turnover, uptake and resting release. These actions may in part underlie the potentiation of inhibitory transmission and the depression of excitatory transmission by pentobarbital.