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Activation of a glycine transporter on spinal cord neurons causes enhanced glutamate release in a mouse model of amyotrophic lateral sclerosis
Author(s) -
Raiteri Luca,
Paolucci Egle,
Prisco Simona,
Raiteri Maurizio,
Bonanno Giambattista
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705142
Subject(s) - strychnine , glycine receptor , glycine , amyotrophic lateral sclerosis , sod1 , spinal cord , glutamate receptor , pharmacology , chemistry , nmda receptor , amino acid , medicine , biochemistry , neuroscience , biology , receptor , disease
The release of [ 3 H] D ‐aspartate ([ 3 H] D ‐ASP) or [ 3 H]GABA evoked by glycine from spinal cord synaptosomes was compared in mice expressing mutant human SOD1 with a Gly 93 Ala substitution ([SOD1‐G93A(+)]), a transgenic model of amyotrophic lateral sclerosis, and in control mice. Mice expressing mutated SOD1 were killed at the advanced phase of the pathology, when they showed signs of ingestion disability, because of paralysis of the posterior limbs. In control mice glycine concentration‐dependently evoked [ 3 H] D ‐ASP and [ 3 H]GABA release. Potentiation of the spontaneous release of both amino acids is likely to be mediated by activation of a glycine transporter, since the effects of glycine were counteracted by the glycine transporter blocker glycyldodecylamide but not by the glycine receptor antagonists strychnine and 5,7‐dichlorokynurenate. The glycine‐evoked release of [ 3 H] D ‐ASP, but not that of [ 3 H]GABA, was significantly more pronounced in SOD1‐G93A(+) than in control animals. British Journal of Pharmacology (2003) 138 , 1021–1025. doi: 10.1038/sj.bjp.0705142