KINETICS OF <i>IN VIVO</i> CONVERSION OF γ‐[³H]AMINOBUTYRIC ACID TO γ‐[³H]HYDROXYBUTYRIC ACID BY RAT BRAIN^1,²

Abstract

Abstract— The appearance of γ‐[ 3 H]hydroxybutyric acid ([ 3 H]GHB) in rat brain at various times after the intraventricular administration of [ 3 H]GABA was determined. Radioactivity recovered as [ 3 H]GHB was maximal 30 s after [ 3 H]GABA administration and declined exponentially thereafter. From a linear transformation of the disappearance with time of [ 3 H]GHB formed from [ 3 H]GABA, the fractional rate of disappearance and turnover time of GHB were calculated. Administration of amino‐oxyacetic acid (50 mg/kg i.p.) 1 h before [ 3 H]GABA, reduced [ 3 H]GHB formation, measured 4 min after [ 3 H]GABA, to 28% of that found in control animals. This strongly suggests that GABA‐transaminase catalyzes at least one step in the conversion pathway. [ 3 H]GHB recoverable 4 min after [ 3 H]GABA was unchanged when animals were pretreated with pyrazole (1.25–5.0 mmol/kg), diphenyl‐hydantoin (25 and 75 mg/kg), phenobarbital (7.5–60 mg/kg), ethanol (1.25–5.0 g/kg), or morphine (2.5–10 mg/kg). Significantly more [ 3 H]GHB could be recovered at several time points from animals which had been pretreated with 50 mg/kg i.p. of the convulsant 3‐mercaptopropionic acid.