In vivo detection of cortical GABA turnover from intravenously infused [1-13C]D-glucose.
In this study [2-(13)C] gamma-aminobutyric acid (GABA) was spectrally resolved in vivo and detected simultaneously with [4-(13)C]glutamate (Glu) and [4-(13)C]glutamine (Gln) in the proton spectra obtained from a localized 40 microL voxel in rat neocortex with the use of an adiabatic (1)H-observed, (13)C-edited (POCE) spectroscopy method and an 89-mm-bore vertical 11.7 Tesla microimager. The time-resolved kinetics of (13)C label incorporation from intravenously infused [1-(13)C]glucose into [4-(13)C]Glu, [4-(13)C]Gln, and [2-(13)C]GABA were measured after acute administration of gabaculine, a potent and specific inhibitor of GABA-transaminase. In contrast to previous observations of a rapid turnover of [2-(13)C]GABA from [1-(13)C]glucose in intact rat brain, the rate of (13)C incorporation from [1-(13)C]glucose into [2-(13)C]GABA in the gabaculine-treated rats was found to be significantly reduced as a result of the blockade of the GABA shunt.
Yang
Jehoon
J
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Li
Charles Q
CQ
Shen
Jun
J
D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007262:Infusions, Intravenous; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D002247:Carbon Isotopes; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D005971:Glutamates; D005973:Glutamine; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D005947:Glucose