Measurement of GABA following GABA-transaminase inhibition by gabaculine: a 1H and 31P NMR spectroscopic study of rat brain in vivo.
A selective 1H NMR spin-echo editing method was used to detect the 4-CH2 of GABA in rat brain in vivo before and after intravenous administration of the highly selective GABA transaminase inhibitor, gabaculine (3-amino-2,3-dihydrobenzoic acid-HCl; 100 mg/kg, intravenously). The effects of the inhibitor on high energy phosphates and pHi were determined by 31P NMR. GABA levels increased approximately linearly (r = 0.81 to 0.94; P < 0.0005) from 1.9 +/- 0.4 mumol/g (pre-gabaculine; mean +/- SD) to between 6 and 8 mumol/g after 4 hr at rates of accumulation of 1.1 to 2.9 mumol/hr/g. 1H NMR spectroscopic measurements of cerebral GABA and its rate of turnover offers a new approach in the study of GABA-mediated processes in vivo.
Behar
K L
KL
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520-8024.
Boehm
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D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003401:Creatine / Q000032:analysis / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005971:Glutamates / Q000032:analysis / Q000378:metabolism; D018698:Glutamic Acid; D006859:Hydrogen; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009711:Nucleotides / Q000032:analysis / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000378:metabolism
D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; D009711:Nucleotides; D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D001224:Aspartic Acid; C012987:gabaculine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006859:Hydrogen; C000179:N-acetylaspartate; D000612:4-Aminobutyrate Transaminase; D003401:Creatine