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Inhibition of the glutamate transporter and glial enzymes in rat striatum by the gliotoxin, ocaminoadipate
Author(s) -
McBean Gethin J.
Publication year - 1994
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 - 10.1111/j.1476-5381.1994.tb17022.x
Subject(s) - glutamine synthetase , convulsant , biochemistry , enzyme , glutamate receptor , glutamine , chemistry , methionine , gliotoxin , biology , amino acid , receptor , aspergillus fumigatus , microbiology and biotechnology
1 The effect of the gliotoxic analogue of glutamate, ocaminoadipate, on the high affinity transport of D‐[ 3 H]‐aspartate into a crude striatal P 2 preparation, and on the activity of two enzymes of which glutamate is the substrate has been examined. 2 The L‐isomer of ocaminoadipate competitively inhibited the transport protein, with a K i value of 192 μ m , whereas the D‐isomer of ocaminoadipate was ineffective. The potent convulsant, L‐methionine‐ S ‐sulphoximine, was also without effect on the activity of the gluatmate transport protein. 3 L‐αAminoadipate was a competitive inhibitor of both glutamine synthetase, and γ‐glutamylcysteine synthetase, with K i values of 209 μ m and 7 m m respectively. Once again, the D‐isomer of ocaminoadipate was a far weaker inhibitor of either enzyme. 4 The results are discussed in terms of the mechanism of action of ocaminoadipate in causing toxicity of glial cells.