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BACLOFEN: EFFECTS ON AMINO ACID RELEASE AND METABOLISM IN SLICES OF GUINEA PIG CEREBRAL CORTEX
Author(s) -
Potashner S. J.
Publication year - 1979
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1979.tb04516.x
Subject(s) - glycine , glutamate receptor , glutamine , alanine , baclofen , inhibitory postsynaptic potential , amino acid , excitatory postsynaptic potential , chemistry , biochemistry , neurotransmission , stimulation , serine , metabolism , biology , neuroscience , receptor , agonist , phosphorylation
Slices of guinea‐pig cerebral cortex were used to investigate the effects of the antispastic drug β ‐( p ‐chlorophenyl)‐γ‐aminobutyrate (Baclofen, Lioresal) on the release and metabolism of several amino acids. Electrical stimulation of slices evoked (1) a relatively large release, probably from nerve terminals, of 14 C‐labelled tissue glumate, aspartate and γ‐aminobutyrate (GABA) synthesized via metabolism of D‐[U‐ 14 C]glucose and (2) a relatively small release, probably not from nerve terminals, of 14 C‐labelled tissue alanine and threonine‐serine‐glutamine and of exogenous radiolabeled glutamate, aspartate, GABA and α‐aminoisobutyrate that had been taken up from the medium. Baclofen (4μM) preferentially inhibited the release of 14 C‐labelled tissue glutamate and aspartate. It had no effect on the concentrations and specific radio‐activities of most of the labelled tissue amino acids in the slices. However, it increased the turnover of 14 C‐labelled tissue glycine approx 4‐fold and elevated the specific radio activity of tissue alanine by 40%. It was concluded that Baclofen affects transmission not by modulating the release of the inhibitory amino acid GABA, but by selectively suppressing the release of the excitatory amino acids glutamate and aspartate from nerve terminals. Provided that this action obtains in the spinal cord, it may at least partly underlie the antispastic action of Baclofen as glutamate and aspartate are presumed to be the transmitters released from terminals of non‐nociceptive primary afferent fibers and excitatory interneurons, respectively. The Baclofen‐induced increase in glycine turnover suggests an additional effect on inhibitory glycinergic interneurons in the spinal cord.