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PRECONVULSIVE CHANGES IN BRAIN GLUCOSE METABOLISM FOLLOWING DRUGS INHIBITING GLUTAMATE DECARBOXYLASE
Author(s) -
Horton R. W.,
Meldrum B. S.
Publication year - 1976
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.1471-4159.1976.tb04454.x-i1
Subject(s) - glycogen , chemistry , endocrinology , medicine , isoniazid , methionine , metabolism , biochemistry , biology , amino acid , tuberculosis , pathology
—Brain glucose and glycogen concentrations have been studied in mice treated with allylglycine, 4‐deoxypyridoxine and isoniazid, and the effects compared with the preconvulsive increase in brain glucose and glycogen concentration that follows d , l ‐methionine sulphoximine treatment. Allylglycine (180 mg/kg), 4‐deoxypyridoxine (250 mg/kg), isoniazid (150 mg/kg) and d , l ‐methionine sulphoximine (300 mg/kg) when given to mice at room temperature, cause a fall in rectal temperature which can be prevented by maintaining the mice in an incubator at 33‐34°C. An increase in brain glucose concentration is seen after allylglycine (+ 133%), d , l ‐methionine sulphoximine (+ 113%) and 4‐deoxypyridoxine (+ 70%) treatment when mice are kept at room temperature and killed before convulsions occur. This is associated with a rise in blood glucose concentration after allylglycine, but not after the other drugs. Preventing the fall in rectal temperature reduces, but does not abolish, the rise in brain glucose concentration seen after allylglycine, d , l ‐methionine sulphoximine and 4‐deoxypyridoxine. Brain glycogen concentration increases at room temperature after D,L‐methionine sulphoximine and 4‐deoxypyridoxine, but in mice with maintained body temperature only 4‐deoxypyridoxine produces an increase in brain glycogen. Isoniazid does not increase brain glucose or glycogen at room temperature, but reduces their concentration in mice kept in the incubator. All four drugs are known to act on amino acid metabolism; d , l ‐methionine sulphoximine potently inhibits glutamine synthetase whereas 4‐deoxypyridoxine, allylglycine and isoniazid inhibit glutamate decarboxylase. The connection, if any, between a block in the further metabolism of glutamate and an increase in brain glucose and glycogen is unknown.