Baclofen: effects on amino acid release

Abstract

This study investigated the effects of the antispastic drug β-(p-chlorophenyl)-γ-amino-butyric acid (Baclofen) on the release of amino acids from slices of guinea pig cerebral cortex. Electrical stimulation of slices evoked the release of endogenous 14 C-labelled glutamate, aspartate, γ-aminobutyric acid (GABA), alanine, and threonine–serine–glutamine (labelled via metabolism of D-[U- 14 C]glucose), and of exogenous glutamate, aspartate, GABA, and α-aminoisobutyrate. The releases of endogenous 14 C-labelled glutamate, aspartate, and GABA were three to seven times larger than those of other amino acids. Baclofen (4 μM) inhibited the evoked release of endogenous 14 C-labelled glutamate and aspartate by nearly 60%, that of endogenous 14 C-labelled threonine–serine–glutamine and alanine by 14–19%, but had no effect on that of endogenous 14 C-labelled GABA. The drug inhibited the evoked release of the exogenous amino acids by 25–32%. Baclofen doubled the incorporation of 14 C from D-[U- 14 C]glucose into endogenous alanine but was without effect on either the incorporation of 14 C into the other endogenous amino acids or the turnover of any of the endogenous 14 C-labelled amino acids. Because endogenous 14 C-labelled glutamate, aspartate, and GABA are probably released from nerve terminals, Baclofen selectively suppresses the release of excitatory amino acids from nerve terminals. Similarly, depression of the release of excitatory transmitter (presumably glutamate) from primary afferent terminals in the spinal cord may at least partly explain the antispastic action of Baclofen.