Effect of antivitamin B6 on regional GABA metabolism in mouse brain and its relation to convulsions.
The effects of administration of DL-penicillamine (PeA), thiosemicarbazide (TSC), semicarbazide-HCl (SC) as convulsants and pyridoxine (PN) as anticonvulsant on gamma-aminobutyric acid (GABA) content, glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) activities in cerebral cortex, striatum, diencephalon, mesencephalon, cerebellum and pons/medulla were investigated. The onset of convulsions induced by these convulsants coincides with the fall in GABA content and GAD activity in the mesencephalon area, and in contrast, the cessation of the convulsions by PN supplement coincides with the recovery in both the parameters. Aminooxyacetic acid (AOAA), a potent GABA-elevating agent showed an anticonvulsant property against convulsion by TSC for several hours after the injection of AOAA, but lost this property 16 hr after the treatment. The TSC administration 16 hr after the AOAA pretreatment significantly decreased the GABA content in all the regions, particularly in the mesencephalon and diencephalon areas, which had been elevated by the AOAA pretreatment, together with its ability to induce convulsion. FRom the above results it may be postulated that the critical drop of GABA level from a plateau to another lower level following the decrease of GAD activity in the mesencephalon area is an important factor in the induction of convulsion.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D010396:Penicillamine / Q000494:pharmacology*; D011736:Pyridoxine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012663:Semicarbazides / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012663:Semicarbazides; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; C005151:thiosemicarbazide; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010396:Penicillamine; D011736:Pyridoxine