Combined Effects of a Metabolic Inhibitor (Gabaculine) and an Uptake Inhibitor (Ketamine) on the γ‐Aminobutyrate System in Mouse Brain

J. D. Wood, J. W. Geddes, S. ‐K Tsui, E. Kurylo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Abstract: The intramuscular administration of a γ‐aminobutyrate‐α‐oxoglutarate aminotransferase (GABA‐T) inhibitor, gabaculine, to mice resulted in significant increases in GABA content and decreases in the content of aspartate, glutamate, and glutamine in the nerve endings (synaptosomes). These effects were ameliorated by the concurrent administration of the GABA uptake inhibitor ketamine. A major cause of these effects was the gabaculine‐induced inhibition of GABA‐T activity and the lessening of this inhibition by ketamine. The latter phenomenon was not due to a direct action of ketamine on the enzyme, nor to an interaction between gabaculine and ketamine. Rather, it appeared that ketamine might be interfering with the transport of gabaculine into the cellular structures. The anticonvulsant action of the GABA‐T inhibitor and the GABA uptake inhibitor together was little different from that of the GABA‐T inhibitor alone.

Original languageEnglish
Pages (from-to)1710-1715
Number of pages6
JournalJournal of Neurochemistry
Volume39
Issue number6
DOIs
StatePublished - Dec 1982

Keywords

  • Convulsions
  • Gabaculine
  • Ketamine
  • γ‐Aminobutyrate uptake
  • γ‐Aminobutyrate‐α‐oxoglutarate aminotransferase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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