EFFECTS OF CHRONIC ORAL TREATMENT WITH GABA-TRANSAMINASE INHIBITORS ON THE GABA SYSTEM IN BRAIN, LIVER, KIDNEY, AND PLASMA OF THE RAT

The inhibitory neurotransmitter gamma-aminoburyric acid (GABA) is not solely located in the CNS, it and the enzymes responsible for its synt hesis (glutamic acid decarboxylase, GAD, EC 4.1.1.15) and catabolism ( GABA-transaminase, GABA-T, EC 2.6.1.19) are also present in non-neuron al Following 2, 8 and 21 day oral administration of ethanolamine-O-sul phate (EOS) and gamma-vinyl GABA (GVG), two irreversible inhibitors of GABA-T, the GABA content and activities of GAD and GABA-T in rat brai n, liver and kidney, and the GABA content of plasma were determined. G ABA-T activity was significantly decreased (over 80%) in liver, brain and kidney, although there was 2-3 times the residual activity left in the brain compared with the peripheral organs. GABA content was subse quently significantly elevated in the liver (300-1500%), plasma (200-3 00%) and brain (200-300%), although, surprisingly, the kidney GABA con tent was reduced (by 60-70%) compared with control. GAD activity was d ecreased following 8 day treatment in liver and brain. Kidney GAD was reduced at all time points. These two compounds are anticonvulsant, GV G is used clinically for the treatment of epilepsy but it seems that t hese drugs have significant peripheral effects. Copyright (C) 1996 Els evier Science Inc.