Evidence using in vivo microdialysis that aminotransferase activities are important in the regulation of the pools of transmitter amino acids.
The effect of aminooxyacetic acid (AOAA), an inhibitor of pyridoxal phosphate-dependent enzymes (including the aminotransferases), on the K(+)-evoked release of amino acids was studied during microdialysis of neostriatum in anesthetized rats. K(+)-evoked (100 mM) release of aspartate, glutamate, and GABA was inhibited by 74%, 70%, and 63%, respectively, by 20 mM Mg2+ and are therefore reflecting release from the transmitter pools of these amino acids. Treatment with AOAA decreased the K(+)-evoked release of aspartate, glutamate, and GABA instantly, with a delayed decrease in the efflux of glutamine and alanine, arguing that the synthesis of transmitter amino acids in particular is sensitive to the activity of pyridoxal phosphate-dependent enzymes. Interestingly, GABA release increased severalfold following the initial decrease, probably reflecting inhibition by AOAA on GABA aminotransferase, the enzyme most sensitive to inhibition by AOAA, and responsible for enzymatic inactivation of transmitter GABA.
Bakkelund
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AH
Division for Environmental Toxicology, NDRE, Kjeller, Norway.
Fonnum
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Paulsen
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D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003956:Dialysis; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D005973:Glutamine; D000625:Aminooxyacetic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000637:Transaminases; D000409:Alanine; D011188:Potassium