In vivo conversion of gamma-aminobutyric acid and 1,4-butanediol to gamma-hydroxybutyric acid in rat brain. Studies using stable isotopes.
The formation of 4-[1,4-13C]hydroxybutyric acid ([13C]gamma-hydroxybutyric acid; [13C]GHB) in rat brain was studied following intracerebroventricular (i.c.v.) administration of either 4-[1,4-13C]aminobutyric acid ([13C]GABA or 1,4-[1,4-13C]butanediol ([13C]1,4-BD) to awake, freely moving animals. GHB and [13C]GHB were measured with a gas chromatographic mass spectrometric (GC/MS) technique designed to detect the lactone derivative of GHB with the acid or lactone being determined by conditions of tissue extraction. [13C]GHB was detected following i.c.v. administration of [13C]GABA with a turnover rate of 2.04 nmol/g tissue/hr and [13C]1,4-BD with a turnover rate of 1.4 nmol/g/hr. The formation of [13C]GHB from [13C]GABA was blocked by an inhibitor of GABA-transaminase, but this drug had no effect on the formation of [13C]GHB from [13C]1,4-BD. The latter pathway was also unaffected by alcohol dehydrogenase inhibitors, compounds which block this pathway in the periphery. Further, in the course of these experiments, naturally occurring endogenous gamma-butyrolactone (GBL) was detected in rat brain in a concentration of 200 pmol/g tissue weight, but lactonization in vivo of [13C]GHB formed from either labeled GABA or 1,4-BD was not demonstrated. These data confirm two separate pathways of synthesis for GHB in brain, demonstrate the presence of GBL in brain, and illustrate the utility of a new GC/MS technique for analysis of GHB and for GBL which does not involve extensive derivatization.
Snead
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Department of Pediatrics, University of Alabama, School of Medicine, Birmingham.
Furner
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Liu
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D002072:Butylene Glycols / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D007700:Kinetics; D007783:Lactones / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012978:Sodium Oxybate / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002072:Butylene Glycols; D006885:Hydroxybutyrates; D007783:Lactones; D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; C039681:1,4-butanediol