Endogenous gamma-hydroxybutyrate in rat brain areas: postmortem changes and effects of drugs interfering with gamma-aminobutyric acid metabolism.
The possibility that gamma-hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), may play a role in the CNS has recently come to attention. We describe here a sensitive and specific mass fragmentographic technique that allows the measurement of picomole amounts of GHB in single rat brain areas. Moreover, we show that GHB can accumulate postmortem, an effect that is blocked by the use of microwave irradiation to kill the animals. To understand further the relationship between GABA and GHB formation, we treated rats with drugs known to interfere with GABA metabolism at different levels and concomitantly measured GABA and GHB in cerebral cortex and cerebellum. Isoniazide, which blocks the formation of GABA, also decreases GHB. Blockers of the catabolism of GABA, such as aminooxyacetic acid and gamma-acetylenic GABA, increase GABA levels and decrease those of GHB. Sodium dipropylacetate increases both GABA and GHB, supporting the hypothesis that this effective antiepileptic drug also blocks in vivo the enzyme that converts succinic semialdehyde to succinic acid.
D000480:Alkynes; D000614:Aminocaproates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006885:Hydroxybutyrates / Q000378:metabolism*; D007538:Isoniazid / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011180:Postmortem Changes; D051381:Rats; D011919:Rats, Inbred Strains; D012978:Sodium Oxybate / Q000378:metabolism*; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000480:Alkynes; D000614:Aminocaproates; D006885:Hydroxybutyrates; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; C013785:4-amino-5-hexynoic acid; D012978:Sodium Oxybate; D007538:Isoniazid